Mutagenetix > Incidental Mutation

Incidental Mutation 'R5296:Cacna1s'

405388

Institutional Source

Beutler Lab

Gene Symbol

Cacna1s

Ensembl Gene

ENSMUSG00000026407

Gene Name

calcium channel, voltage-dependent, L type, alpha 1S subunit

Synonyms

sj, mdg, muscle dysgenesis, DHPR alpha1s, Cav1.1, Cchl1a3, fmd

MMRRC Submission

042879-MU

Accession Numbers

Genbank: NM_001081023; MGI: 88294

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R5296 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

136052750-136119822 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 136095785 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Valine to Methionine at position 674 (V674M)

Ref Sequence

ENSEMBL: ENSMUSP00000125262 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000112064] [ENSMUST00000112068] [ENSMUST00000160641] [ENSMUST00000161865]

AlphaFold

no structure available at present

Predicted Effect

probably benign
Transcript: ENSMUST00000112064
AA Change: V921M

PolyPhen 2 Score 0.107 (Sensitivity: 0.93; Specificity: 0.86)

SMART Domains

Protein: ENSMUSP00000107695
Gene: ENSMUSG00000026407
AA Change: V921M

Domain	Start	End	E-Value	Type
Pfam:Ion_trans	50	345	4.3e-68	PFAM
Pfam:Ion_trans	431	672	4.5e-56	PFAM
Pfam:PKD_channel	516	667	1.9e-7	PFAM
low complexity region	675	685	N/A	INTRINSIC
low complexity region	740	756	N/A	INTRINSIC
Pfam:Ion_trans	798	1076	2.6e-65	PFAM
Pfam:Ion_trans	1117	1392	1.2e-71	PFAM
Pfam:PKD_channel	1126	1387	8.4e-13	PFAM
Pfam:GPHH	1394	1463	2.3e-38	PFAM
Ca_chan_IQ	1515	1548	3.71e-14	SMART
low complexity region	1657	1669	N/A	INTRINSIC
Pfam:CAC1F_C	1756	1845	2.8e-8	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000112068
AA Change: V921M

PolyPhen 2 Score 0.107 (Sensitivity: 0.93; Specificity: 0.86)

SMART Domains

Protein: ENSMUSP00000107699
Gene: ENSMUSG00000026407
AA Change: V921M

Domain	Start	End	E-Value	Type
Pfam:Ion_trans	88	333	9.1e-57	PFAM
PDB:4DEY\|B	334	417	1e-20	PDB
Pfam:Ion_trans	466	660	3.7e-46	PFAM
Pfam:PKD_channel	513	667	6.7e-7	PFAM
low complexity region	675	685	N/A	INTRINSIC
low complexity region	740	756	N/A	INTRINSIC
low complexity region	804	818	N/A	INTRINSIC
Pfam:Ion_trans	834	1064	3.9e-53	PFAM
Pfam:Ion_trans	1152	1361	6.7e-66	PFAM
Pfam:PKD_channel	1201	1368	8.4e-10	PFAM
Blast:EFh	1382	1410	5e-8	BLAST
Ca_chan_IQ	1496	1529	3.71e-14	SMART
low complexity region	1638	1650	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000160641
AA Change: V921M

PolyPhen 2 Score 0.107 (Sensitivity: 0.93; Specificity: 0.86)

SMART Domains

Protein: ENSMUSP00000125278
Gene: ENSMUSG00000026407
AA Change: V921M

Domain	Start	End	E-Value	Type
Pfam:Ion_trans	88	333	9.3e-57	PFAM
PDB:4DEY\|B	334	417	1e-20	PDB
Pfam:Ion_trans	466	660	3.8e-46	PFAM
Pfam:PKD_channel	513	667	6.7e-7	PFAM
low complexity region	675	685	N/A	INTRINSIC
low complexity region	740	756	N/A	INTRINSIC
low complexity region	804	818	N/A	INTRINSIC
Pfam:Ion_trans	834	1064	4e-53	PFAM
Pfam:PKD_channel	1126	1387	6.1e-12	PFAM
Pfam:Ion_trans	1152	1380	9e-65	PFAM
Blast:EFh	1401	1429	5e-8	BLAST
Ca_chan_IQ	1515	1548	3.71e-14	SMART
low complexity region	1657	1669	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000161865
AA Change: V674M

PolyPhen 2 Score 0.107 (Sensitivity: 0.93; Specificity: 0.86)

SMART Domains

Protein: ENSMUSP00000125262
Gene: ENSMUSG00000026407
AA Change: V674M

Domain	Start	End	E-Value	Type
Pfam:Ion_trans	3	98	1.1e-21	PFAM
Pfam:Ion_trans	184	425	3.3e-56	PFAM
Pfam:PKD_channel	267	420	1.8e-7	PFAM
low complexity region	428	438	N/A	INTRINSIC
low complexity region	493	509	N/A	INTRINSIC
Pfam:Ion_trans	551	829	1.9e-65	PFAM
Pfam:Ion_trans	870	1126	5.4e-72	PFAM
Pfam:PKD_channel	954	1121	7.2e-10	PFAM
Pfam:GPHH	1128	1197	1.8e-38	PFAM
Ca_chan_IQ	1249	1282	3.71e-14	SMART
low complexity region	1391	1403	N/A	INTRINSIC

Meta Mutation Damage Score

0.0898

Coding Region Coverage

1x: 99.5%
3x: 98.9%
10x: 97.9%
20x: 96.6%

Validation Efficiency

100% (65/65)

MGI Phenotype

Strain: 1856326
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes one of the five subunits of the slowly inactivating L-type voltage-dependent calcium channel in skeletal muscle cells. Mutations in this gene have been associated with hypokalemic periodic paralysis, thyrotoxic periodic paralysis and malignant hyperthermia susceptibility. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygous mutants show edema and failure of myoblast differentiation by day 13 of embryonic development and die perinatally. All muscles degenerate and additional secondary anomalies of the skeleton, short jaw, and cleft palate are seen. [provided by MGI curators]

Allele List at MGI

All alleles(4) : Targeted(3) Spontaneous(1)

Other mutations in this stock

Total: 57 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Apobr	A	C	7: 126,588,024	D89A	probably damaging	Het
Bhlhe41	C	T	6: 145,862,968		probably benign	Het
Cavin2	T	C	1: 51,289,870		probably null	Het
Cd300lb	T	C	11: 114,924,937	S106G	possibly damaging	Het
Ceacam15	A	G	7: 16,673,196	V132A	probably benign	Het
Ddi2	G	T	4: 141,684,765	Q279K	probably benign	Het
Dnah11	A	G	12: 117,883,416	V4304A	probably damaging	Het
Dnah2	C	T	11: 69,458,920	R2399Q	probably benign	Het
Dnase1l1	C	T	X: 74,277,038		probably null	Het
Epsti1	T	A	14: 77,904,650	H55Q	probably benign	Het
Flad1	T	C	3: 89,411,196	T17A	probably damaging	Het
Fzd2	C	T	11: 102,606,155	T475M	probably damaging	Het
Gemin5	C	A	11: 58,130,061	W1099L	probably damaging	Het
Gm8979	A	T	7: 106,081,848		noncoding transcript	Het
Gm9892	T	C	8: 52,196,929		noncoding transcript	Het
Gmeb2	A	G	2: 181,255,986		probably benign	Het
Grip1	A	G	10: 119,929,928	E55G	probably damaging	Het
Hltf	T	C	3: 20,108,112	S825P	probably damaging	Het
Kcnh3	A	T	15: 99,241,939	Q902L	probably null	Het
Kcnt2	C	T	1: 140,609,615	P1037L	probably damaging	Het
Klhl18	G	C	9: 110,436,127	N335K	possibly damaging	Het
Lama5	A	C	2: 180,193,801	L1253R	probably damaging	Het
Lancl2	T	G	6: 57,724,582	S230A	probably benign	Het
Lmcd1	A	G	6: 112,315,588	M134V	probably damaging	Het
Lrrc23	C	A	6: 124,774,482	A205S	probably damaging	Het
Mfsd13b	T	A	7: 120,991,738	I234N	probably damaging	Het
Mroh3	A	G	1: 136,196,323	S386P	probably damaging	Het
Mylk3	A	C	8: 85,355,431	F313V	possibly damaging	Het
Myo9b	A	T	8: 71,333,388	Q643L	possibly damaging	Het
Nacad	T	C	11: 6,605,745	S2G	unknown	Het
Olfr1269	A	T	2: 90,118,699	W300R	probably damaging	Het
Olfr136	C	T	17: 38,335,456	Q100*	probably null	Het
Olfr419	G	T	1: 174,250,756	T57K	possibly damaging	Het
Olfr908	T	C	9: 38,516,116	F28S	probably damaging	Het
Pkd1	T	C	17: 24,576,074	V2245A	probably damaging	Het
Pkdrej	G	A	15: 85,817,118	T1539I	possibly damaging	Het
Plch2	G	T	4: 154,989,999		probably null	Het
Pygm	G	A	19: 6,384,579	R34H	probably damaging	Het
Rgs12	T	C	5: 35,021,104		probably benign	Het
Ruvbl1	T	C	6: 88,485,908	I338T	probably damaging	Het
Sapcd1	T	A	17: 35,026,731	Q104L	probably damaging	Het
Satb2	T	C	1: 56,796,907	E575G	probably damaging	Het
Sema6b	T	A	17: 56,127,091		probably null	Het
Slc25a11	T	C	11: 70,646,185	N15D	probably damaging	Het
Slc26a6	C	T	9: 108,860,646	T526M	probably damaging	Het
Tcaf3	G	T	6: 42,587,510	T906K	possibly damaging	Het
Thbd	A	T	2: 148,406,983	C322S	probably damaging	Het
Traf2	A	G	2: 25,520,440	L399P	probably damaging	Het
Troap	T	A	15: 99,078,817	V274D	probably damaging	Het
Utrn	G	A	10: 12,401,355	T3406M	probably damaging	Het
Uts2	G	T	4: 150,999,051	A40S	possibly damaging	Het
Vmn2r109	T	A	17: 20,554,341	I251F	possibly damaging	Het
Vmn2r67	A	G	7: 85,137,022	S592P	probably damaging	Het
Vps13b	T	G	15: 35,876,413	W2797G	probably damaging	Het
Ythdf1	A	T	2: 180,912,188	M51K	probably damaging	Het
Zfp60	T	A	7: 27,738,530		probably benign	Het
Zfp882	T	A	8: 71,914,360	F344I	probably damaging	Het

Other mutations in Cacna1s

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00336:Cacna1s	APN	1	136084273	nonsense	probably null
IGL00517:Cacna1s	APN	1	136087339	missense	probably damaging	1.00
IGL01316:Cacna1s	APN	1	136118964	missense	probably benign	0.01
IGL01348:Cacna1s	APN	1	136075152	missense	possibly damaging	0.95
IGL01739:Cacna1s	APN	1	136097132	critical splice donor site	probably null
IGL01773:Cacna1s	APN	1	136118753	missense	probably benign	0.32
IGL02056:Cacna1s	APN	1	136119000	missense	probably benign
IGL02262:Cacna1s	APN	1	136108129	missense	probably damaging	0.98
IGL02324:Cacna1s	APN	1	136075176	splice site	probably benign
IGL02352:Cacna1s	APN	1	136093252	splice site	probably benign
IGL02359:Cacna1s	APN	1	136093252	splice site	probably benign
IGL02370:Cacna1s	APN	1	136085347	missense	probably damaging	1.00
IGL02377:Cacna1s	APN	1	136068994	missense	probably damaging	1.00
IGL02474:Cacna1s	APN	1	136118380	missense	probably benign
IGL02606:Cacna1s	APN	1	136079519	missense	probably damaging	0.99
IGL02833:Cacna1s	APN	1	136071005	missense	probably benign	0.03
IGL02974:Cacna1s	APN	1	136092617	missense	possibly damaging	0.78
IGL03064:Cacna1s	APN	1	136111993	missense	probably damaging	1.00
IGL03093:Cacna1s	APN	1	136116064	missense	probably benign	0.00
IGL03286:Cacna1s	APN	1	136077659	missense	probably benign
brookstone	UTSW	1	136092694	missense	probably benign	0.01
flyfish	UTSW	1	136116061	missense	probably benign	0.21
forelle	UTSW	1	136095858	missense	probably damaging	0.99
river	UTSW	1	136105844	missense	possibly damaging	0.88
stream	UTSW	1	136105814	missense	probably damaging	1.00
BB009:Cacna1s	UTSW	1	136084359	missense	probably damaging	0.99
BB019:Cacna1s	UTSW	1	136084359	missense	probably damaging	0.99
G1Funyon:Cacna1s	UTSW	1	136073441	unclassified	probably benign
N/A:Cacna1s	UTSW	1	136073509	missense	probably benign	0.00
R0030:Cacna1s	UTSW	1	136094989	critical splice donor site	probably null
R0030:Cacna1s	UTSW	1	136094989	critical splice donor site	probably null
R0097:Cacna1s	UTSW	1	136100622	missense	possibly damaging	0.79
R0097:Cacna1s	UTSW	1	136100622	missense	possibly damaging	0.79
R0240:Cacna1s	UTSW	1	136073496	unclassified	probably benign
R0255:Cacna1s	UTSW	1	136118806	missense	possibly damaging	0.93
R0302:Cacna1s	UTSW	1	136100604	missense	probably benign	0.01
R0319:Cacna1s	UTSW	1	136070717	missense	probably damaging	0.99
R0411:Cacna1s	UTSW	1	136113303	missense	probably damaging	1.00
R0413:Cacna1s	UTSW	1	136098209	missense	probably benign	0.00
R0482:Cacna1s	UTSW	1	136113394	missense	probably benign
R0491:Cacna1s	UTSW	1	136089008	splice site	probably benign
R0518:Cacna1s	UTSW	1	136076859	missense	probably benign
R0717:Cacna1s	UTSW	1	136098291	missense	probably damaging	1.00
R0725:Cacna1s	UTSW	1	136098526	splice site	probably benign
R0815:Cacna1s	UTSW	1	136112957	missense	possibly damaging	0.95
R1384:Cacna1s	UTSW	1	136094971	missense	probably benign	0.02
R1518:Cacna1s	UTSW	1	136098551	missense	probably damaging	1.00
R1548:Cacna1s	UTSW	1	136110937	missense	probably damaging	1.00
R1725:Cacna1s	UTSW	1	136098623	missense	probably damaging	1.00
R1728:Cacna1s	UTSW	1	136118716	missense	probably benign
R1729:Cacna1s	UTSW	1	136118716	missense	probably benign
R1730:Cacna1s	UTSW	1	136118716	missense	probably benign
R1739:Cacna1s	UTSW	1	136118716	missense	probably benign
R1762:Cacna1s	UTSW	1	136118716	missense	probably benign
R1783:Cacna1s	UTSW	1	136118716	missense	probably benign
R1784:Cacna1s	UTSW	1	136118716	missense	probably benign
R1785:Cacna1s	UTSW	1	136118716	missense	probably benign
R1800:Cacna1s	UTSW	1	136076854	missense	probably benign
R1924:Cacna1s	UTSW	1	136089017	splice site	probably null
R1969:Cacna1s	UTSW	1	136119095	missense	probably benign	0.42
R2072:Cacna1s	UTSW	1	136079504	missense	probably benign
R2380:Cacna1s	UTSW	1	136095848	missense	probably damaging	1.00
R3110:Cacna1s	UTSW	1	136075093	nonsense	probably null
R3112:Cacna1s	UTSW	1	136075093	nonsense	probably null
R3151:Cacna1s	UTSW	1	136105794	missense	probably damaging	1.00
R3696:Cacna1s	UTSW	1	136105814	missense	probably damaging	1.00
R3722:Cacna1s	UTSW	1	136069042	missense	possibly damaging	0.77
R3804:Cacna1s	UTSW	1	136107018	missense	possibly damaging	0.85
R3813:Cacna1s	UTSW	1	136085347	missense	probably damaging	1.00
R3905:Cacna1s	UTSW	1	136084269	missense	probably damaging	0.99
R3907:Cacna1s	UTSW	1	136084269	missense	probably damaging	0.99
R3909:Cacna1s	UTSW	1	136084269	missense	probably damaging	0.99
R4170:Cacna1s	UTSW	1	136108195	missense	probably damaging	1.00
R4329:Cacna1s	UTSW	1	136119033	missense	probably benign	0.00
R4485:Cacna1s	UTSW	1	136076852	missense	probably damaging	1.00
R4581:Cacna1s	UTSW	1	136070970	splice site	probably null
R4719:Cacna1s	UTSW	1	136118652	splice site	probably benign
R4816:Cacna1s	UTSW	1	136115269	missense	possibly damaging	0.89
R4909:Cacna1s	UTSW	1	136079604	missense	probably damaging	0.99
R4917:Cacna1s	UTSW	1	136101564	critical splice donor site	probably null
R5411:Cacna1s	UTSW	1	136105811	missense	probably benign	0.09
R5503:Cacna1s	UTSW	1	136086742	missense	probably damaging	1.00
R5533:Cacna1s	UTSW	1	136098375	critical splice donor site	probably null
R5714:Cacna1s	UTSW	1	136112066	missense	probably benign	0.44
R5775:Cacna1s	UTSW	1	136108122	missense	probably damaging	1.00
R5814:Cacna1s	UTSW	1	136107142	missense	probably benign	0.31
R5820:Cacna1s	UTSW	1	136079604	missense	probably damaging	1.00
R5822:Cacna1s	UTSW	1	136112078	missense	probably damaging	1.00
R5877:Cacna1s	UTSW	1	136100667	missense	probably damaging	0.99
R5923:Cacna1s	UTSW	1	136076822	missense	possibly damaging	0.79
R6021:Cacna1s	UTSW	1	136106487	missense	probably benign	0.15
R6037:Cacna1s	UTSW	1	136070967	missense	possibly damaging	0.90
R6037:Cacna1s	UTSW	1	136070967	missense	possibly damaging	0.90
R6056:Cacna1s	UTSW	1	136105836	missense	probably damaging	1.00
R6143:Cacna1s	UTSW	1	136076758	missense	probably damaging	0.99
R6222:Cacna1s	UTSW	1	136104622	missense	probably benign	0.00
R6237:Cacna1s	UTSW	1	136105844	missense	possibly damaging	0.88
R6274:Cacna1s	UTSW	1	136089045	missense	probably benign	0.02
R6609:Cacna1s	UTSW	1	136113391	missense	probably benign	0.30
R6626:Cacna1s	UTSW	1	136094965	missense	probably damaging	1.00
R6838:Cacna1s	UTSW	1	136084437	missense	possibly damaging	0.91
R6848:Cacna1s	UTSW	1	136092694	missense	probably benign	0.01
R6849:Cacna1s	UTSW	1	136092694	missense	probably benign	0.01
R6850:Cacna1s	UTSW	1	136092694	missense	probably benign	0.01
R6851:Cacna1s	UTSW	1	136092694	missense	probably benign	0.01
R6868:Cacna1s	UTSW	1	136092694	missense	probably benign	0.01
R6879:Cacna1s	UTSW	1	136115959	missense	probably benign	0.12
R6893:Cacna1s	UTSW	1	136077693	missense	probably benign	0.05
R7017:Cacna1s	UTSW	1	136095858	missense	probably damaging	0.99
R7228:Cacna1s	UTSW	1	136071059	missense	possibly damaging	0.90
R7283:Cacna1s	UTSW	1	136073708	missense	probably damaging	1.00
R7357:Cacna1s	UTSW	1	136071021	missense	probably damaging	0.99
R7385:Cacna1s	UTSW	1	136092633	missense	probably damaging	0.99
R7421:Cacna1s	UTSW	1	136086802	missense	probably damaging	1.00
R7505:Cacna1s	UTSW	1	136085449	nonsense	probably null
R7519:Cacna1s	UTSW	1	136070756	missense	probably damaging	0.99
R7675:Cacna1s	UTSW	1	136110874	missense	probably damaging	1.00
R7746:Cacna1s	UTSW	1	136069018	missense	probably damaging	0.99
R7779:Cacna1s	UTSW	1	136119029	missense	probably damaging	1.00
R7850:Cacna1s	UTSW	1	136071048	missense	probably damaging	1.00
R7932:Cacna1s	UTSW	1	136084359	missense	probably damaging	0.99
R7935:Cacna1s	UTSW	1	136092595	missense	possibly damaging	0.62
R7950:Cacna1s	UTSW	1	136100625	missense	probably benign	0.01
R7969:Cacna1s	UTSW	1	136076732	missense	probably damaging	1.00
R8083:Cacna1s	UTSW	1	136095791	missense	possibly damaging	0.91
R8101:Cacna1s	UTSW	1	136118665	missense	probably benign	0.02
R8123:Cacna1s	UTSW	1	136108179	missense	probably damaging	1.00
R8191:Cacna1s	UTSW	1	136108155	missense	probably damaging	1.00
R8194:Cacna1s	UTSW	1	136077692	missense	probably benign	0.33
R8251:Cacna1s	UTSW	1	136086723	missense	probably damaging	1.00
R8265:Cacna1s	UTSW	1	136092626	nonsense	probably null
R8301:Cacna1s	UTSW	1	136073441	unclassified	probably benign
R8310:Cacna1s	UTSW	1	136087337	missense	probably damaging	1.00
R8359:Cacna1s	UTSW	1	136116061	missense	probably benign	0.21
R8461:Cacna1s	UTSW	1	136073702	missense	possibly damaging	0.53
R8553:Cacna1s	UTSW	1	136091802	missense	possibly damaging	0.93
R8743:Cacna1s	UTSW	1	136105548	missense	probably damaging	1.00
R8766:Cacna1s	UTSW	1	136075143	missense	probably damaging	1.00
R8884:Cacna1s	UTSW	1	136115243	missense	probably benign	0.05
R8897:Cacna1s	UTSW	1	136117654	missense	probably benign	0.01
R8939:Cacna1s	UTSW	1	136086806	critical splice donor site	probably null
R8953:Cacna1s	UTSW	1	136097432	missense	possibly damaging	0.94
R9039:Cacna1s	UTSW	1	136088319	missense	probably benign
R9058:Cacna1s	UTSW	1	136070698	nonsense	probably null
R9137:Cacna1s	UTSW	1	136069006	missense	possibly damaging	0.89
R9332:Cacna1s	UTSW	1	136092714	nonsense	probably null
R9416:Cacna1s	UTSW	1	136094951	missense	possibly damaging	0.88
R9427:Cacna1s	UTSW	1	136084352	missense	probably benign	0.30
R9446:Cacna1s	UTSW	1	136117624	missense	probably benign	0.00
R9564:Cacna1s	UTSW	1	136118778	missense	probably benign
R9620:Cacna1s	UTSW	1	136108171	missense	probably damaging	1.00
X0025:Cacna1s	UTSW	1	136115970	missense	probably benign	0.00
Z1176:Cacna1s	UTSW	1	136107084	nonsense	probably null
Z1177:Cacna1s	UTSW	1	136117686	missense	probably benign	0.00

Predicted Primers

PCR Primer
(F):5'- GGTCCTCAGTTCAGATGCTC -3'
(R):5'- ATTCAGAGTCAGTTGCTGTCAC -3'

Sequencing Primer
(F):5'- TCATCTTGTGAGAACGAGGC -3'
(R):5'- ATCTTGCTTGAAGAGGACTGGC -3'

Posted On

2016-07-22