rs79891110

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Pathogenic. The variant received 14 ACMG points: 14P and 0B. PM1PM2PP3_ModeratePP5_Very_Strong

The NM_000719.7(CACNA1C):c.1216G>A(p.Gly406Arg) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,172 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 16/24 in silico tools predict a damaging outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (★★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CACNA1C
NM_000719.7 missense, splice_region

Scores

Splicing: ADA: 0.9697

Clinical Significance

Pathogenic criteria provided, multiple submitters, no conflicts P:11O:2

Conservation

PhyloP100: 10.0

Publications

219 publications found

Variant links:

Genes affected

CACNA1C (HGNC:1390): (calcium voltage-gated channel subunit alpha1 C) This gene encodes an alpha-1 subunit of a voltage-dependent calcium channel. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization. The alpha-1 subunit consists of 24 transmembrane segments and forms the pore through which ions pass into the cell. The calcium channel consists of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. There are multiple isoforms of each of these proteins, either encoded by different genes or the result of alternative splicing of transcripts. The protein encoded by this gene binds to and is inhibited by dihydropyridine. Alternative splicing results in many transcript variants encoding different proteins. Some of the predicted proteins may not produce functional ion channel subunits. [provided by RefSeq, Oct 2012]

CACNA1C Gene-Disease associations (from GenCC):

Timothy syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, G2P, Labcorp Genetics (formerly Invitae)
neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures
Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics
long QT syndrome
Inheritance: AD Classification: MODERATE Submitted by: ClinGen
long QT syndrome 8
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
Brugada syndrome
Inheritance: AD Classification: SUPPORTIVE, NO_KNOWN Submitted by: Orphanet, ClinGen
Brugada syndrome 3
Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
intellectual disability
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
short QT syndrome
Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Ambry Genetics, ClinGen

CACNA1C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 14 ACMG points.

PM1

In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 4 uncertain in NM_000719.7

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.936

PP5

Variant 12-2504944-G-A is Pathogenic according to our data. Variant chr12-2504944-G-A is described in ClinVar as Pathogenic. ClinVar VariationId is 17632.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1C	NM_000719.7 link	c.1216G>A	p.Gly406Arg	missense_variant, splice_region_variant	Exon 8 of 47	ENST00000399655.6	NP_000710.5	Q13936-12
CACNA1C	NM_001167623.2 link	c.1217+405G>A		intron_variant	Intron 8 of 46	ENST00000399603.6	NP_001161095.1	Q13936-37

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CACNA1C	ENST00000399655.6 link	c.1216G>A	p.Gly406Arg	missense_variant, splice_region_variant	Exon 8 of 47	1	NM_000719.7	ENSP00000382563.1	Q13936-12
CACNA1C	ENST00000682544.1 link	c.1306G>A	p.Gly436Arg	missense_variant, splice_region_variant	Exon 8 of 50			ENSP00000507184.1	A0A804HIR0
CACNA1C	ENST00000347598.9 link	c.1216G>A	p.Gly406Arg	missense_variant, splice_region_variant	Exon 8 of 49	1		ENSP00000266376.6	Q13936-11
CACNA1C	ENST00000344100.7 link	c.1216G>A	p.Gly406Arg	missense_variant, splice_region_variant	Exon 8 of 47	1		ENSP00000341092.3	Q13936-14
CACNA1C	ENST00000327702.12 link	c.1216G>A	p.Gly406Arg	missense_variant, splice_region_variant	Exon 8 of 48	1		ENSP00000329877.7	A0A0A0MR67
CACNA1C	ENST00000399638.5 link	c.1216G>A	p.Gly406Arg	missense_variant, splice_region_variant	Exon 8 of 48	1		ENSP00000382547.1	Q13936-31
CACNA1C	ENST00000335762.10 link	c.1216G>A	p.Gly406Arg	missense_variant, splice_region_variant	Exon 8 of 48	5		ENSP00000336982.5	F5H522
CACNA1C	ENST00000399606.5 link	c.1216G>A	p.Gly406Arg	missense_variant, splice_region_variant	Exon 8 of 48	1		ENSP00000382515.1	Q13936-30
CACNA1C	ENST00000399621.5 link	c.1216G>A	p.Gly406Arg	missense_variant, splice_region_variant	Exon 8 of 47	1		ENSP00000382530.1	Q13936-24
CACNA1C	ENST00000399637.5 link	c.1216G>A	p.Gly406Arg	missense_variant, splice_region_variant	Exon 8 of 47	1		ENSP00000382546.1	Q13936-27
CACNA1C	ENST00000402845.7 link	c.1216G>A	p.Gly406Arg	missense_variant, splice_region_variant	Exon 8 of 47	1		ENSP00000385724.3	Q13936-13
CACNA1C	ENST00000399629.5 link	c.1216G>A	p.Gly406Arg	missense_variant, splice_region_variant	Exon 8 of 47	1		ENSP00000382537.1	Q13936-32
CACNA1C	ENST00000682336.1 link	c.1216G>A	p.Gly406Arg	missense_variant, splice_region_variant	Exon 8 of 47			ENSP00000507898.1	A0A804HKE9
CACNA1C	ENST00000399591.5 link	c.1216G>A	p.Gly406Arg	missense_variant, splice_region_variant	Exon 8 of 46	1		ENSP00000382500.1	Q13936-29
CACNA1C	ENST00000399595.5 link	c.1216G>A	p.Gly406Arg	missense_variant, splice_region_variant	Exon 8 of 46	1		ENSP00000382504.1	Q13936-25
CACNA1C	ENST00000399649.5 link	c.1216G>A	p.Gly406Arg	missense_variant, splice_region_variant	Exon 8 of 46	1		ENSP00000382557.1	Q13936-15
CACNA1C	ENST00000399597.5 link	c.1216G>A	p.Gly406Arg	missense_variant, splice_region_variant	Exon 8 of 47	1		ENSP00000382506.1	Q13936-22
CACNA1C	ENST00000399601.5 link	c.1216G>A	p.Gly406Arg	missense_variant, splice_region_variant	Exon 8 of 47	1		ENSP00000382510.1	Q13936-20
CACNA1C	ENST00000399644.5 link	c.1216G>A	p.Gly406Arg	missense_variant, splice_region_variant	Exon 8 of 47	1		ENSP00000382552.1	Q13936-21
CACNA1C	ENST00000683482.1 link	c.1207G>A	p.Gly403Arg	missense_variant, splice_region_variant	Exon 8 of 47			ENSP00000507169.1	Q13936-35
CACNA1C	ENST00000682686.1 link	c.1216G>A	p.Gly406Arg	missense_variant, splice_region_variant	Exon 8 of 46			ENSP00000507309.1	Q13936-19
CACNA1C	ENST00000399603.6 link	c.1217+405G>A		intron_variant	Intron 8 of 46	5	NM_001167623.2	ENSP00000382512.1	Q13936-37
CACNA1C	ENST00000406454.8 link	c.1217+405G>A		intron_variant	Intron 8 of 47	5		ENSP00000385896.3	F5GY28
CACNA1C	ENST00000399634.6 link	c.1217+405G>A		intron_variant	Intron 8 of 46	5		ENSP00000382542.2	E9PDI6
CACNA1C	ENST00000683824.1 link	c.1307+405G>A		intron_variant	Intron 8 of 47			ENSP00000507867.1	A0A804HKC4
CACNA1C	ENST00000399617.6 link	c.1217+405G>A		intron_variant	Intron 8 of 47	5		ENSP00000382526.1	A0A0A0MSA1
CACNA1C	ENST00000682462.1 link	c.1307+405G>A		intron_variant	Intron 8 of 46			ENSP00000507105.1	A0A804HIJ8
CACNA1C	ENST00000683781.1 link	c.1307+405G>A		intron_variant	Intron 8 of 46			ENSP00000507434.1	A0A804HJB6
CACNA1C	ENST00000683840.1 link	c.1307+405G>A		intron_variant	Intron 8 of 46			ENSP00000507612.1	A0A804HJR1
CACNA1C	ENST00000683956.1 link	c.1307+405G>A		intron_variant	Intron 8 of 46			ENSP00000506882.1	A0A804HI37
CACNA1C	ENST00000399641.6 link	c.1217+405G>A		intron_variant	Intron 8 of 46	1		ENSP00000382549.1	Q13936-23
CACNA1C	ENST00000682835.1 link	c.1217+405G>A		intron_variant	Intron 8 of 46			ENSP00000507282.1	A0A804HIZ0
CACNA1C	ENST00000480911.6 link	n.1113+11558G>A		intron_variant	Intron 7 of 26	5		ENSP00000437936.2	F5H638

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152054

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1312642

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

661428

African (AFR)

AF:

0.00

AC:

AN:

30456

American (AMR)

AF:

0.00

AC:

AN:

44402

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25156

East Asian (EAS)

AF:

0.00

AC:

AN:

39042

South Asian (SAS)

AF:

0.00

AC:

AN:

82952

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53286

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5516

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

976280

Other (OTH)

AF:

0.00

AC:

AN:

55552

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74392

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

41532

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000209

AC:

AN:

4780

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67996

Other (OTH)

AF:

0.00

AC:

AN:

2114

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:11Other:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Pathogenic:4

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Apr 25, 2016

Stanford Center for Inherited Cardiovascular Disease, Stanford University

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:provider interpretation

- -

Feb 23, 2024

GeneDx

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); Published functional studies demonstrate G406R reduces channel inactivation, leading to aberrant intracellular calcium levels in multiple tissues (PMID: 15454078); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 19074970, 26822303, 23580742, 27593853, 17224476, 29739816, 30027834, 21910241, 23631430, 23678275, 23313911, 21878566, 28211989, 15454078, 30023270, 22581653, 15863612, 16360093, 28718902, 29845439, 30513141, 30530868, 31737537, 34079780, 28371864, 27034553, 23690510, 31805042, 32161207, 27868338, 30384889, 30998997, 31395954) -

Timothy syndrome

Pathogenic:2Other:1

GeneReviews

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

Classic Timothy syndrome phenotype -

Apr 04, 2018

Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 10, 2011

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Timothy syndrome;C2678478:Brugada syndrome 3;C5774213:Neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures;CN260585:Long qt syndrome 8

Pathogenic:1

Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant, located in the alternatively spliced exon 8A of the CACNA1C gene, is a well-established pathogenic variant that is referenced in the GeneReviews article for CACNA1C-Related Disorders as the predominant cause of classic Timothy syndrome (Napolitano 2021 PMID: 20301577). It has been reported in the literature and in ClinVar in numerous individuals with Timothy syndrome, including several instances of this variant as either de novo or mosaic; additionally, multiple individuals are reported to have inherited this variant from unaffected or mildly affected parents as a result of low-level somatic and/or germline mosaicism (Selected publications: Splawski 2004 PMID: 15454078; Etheridge 2011 PIMD: 21910241; Dufendach 2013 PMID: 23690510; Kawaida 2016 PMID: 27593853; Walsh 2018 PIMD: 28371864; ClinVar Variation ID: 17632). It is present in a single heterozygote in the Genome Aggregation Database (Highest reported MAF: 0.02% [1/4784]; https://gnomad.broadinstitute.org/variant/12-2504944-G-A?dataset=gnomad_r3); please note, disease-causing variants may be present in control databases at low frequencies, reflective of the general population, incomplete penetrance, and/or variable expressivity. In vitro functional studies demonstrate a deleterious effect of this variant on calcium channel function (Selected publications: Splawski 2004 PMID: 15454078; Yarotskyy 2009 PMID: 19074970). A mouse model with this variant recapitulated various abnormal neurodevelopmental features seen in individuals with Timothy syndrome (Bader 2011 PIMD: 21878566). Evolutionary conservation and computational prediction tools strongly support that this variant impacts the protein. In summary, this variant is classified as pathogenic. -

CACNA1C-related disorder

Pathogenic:1

Feb 13, 2019

Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is located in the last amino acid of exon 8. This variant has been previously reported in multiple studies as a de novo heterozygous change in patients with Timothy Syndrome (PMID: 28371864, 23690510, 28211989, 15454078). A functional study showed this variant impairs voltage-dependent channel inactivation causing maintained inward calcium currents (PMID: 15454078). It is absent from the ExAC and gnomAD population databases and thus is presumed to be rare. The c.1216G>A (p.Gly406Arg) variant affects a highly conserved amino acid and is predicted by multiple in silico tools to have a deleterious effect on protein function. Based on the available evidence, the c.1216G>A (p.Gly406Arg) variant is classified as pathogenic. -

Long qt syndrome 8

Pathogenic:1

Feb 16, 2024

Baylor Genetics

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Long QT syndrome

Pathogenic:1

Sep 13, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 406 of the CACNA1C protein (p.Gly406Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Timothy syndrome (PMID: 15454078, 15863612, 21910241, 23578275, 23580742, 23690510, 26227324). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 17632). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). Experimental studies have shown that this missense change affects CACNA1C function (PMID: 15454078, 15863612, 18250309, 19074970, 26822303). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic. -

Cardiovascular phenotype

Pathogenic:1

May 03, 2022

Ambry Genetics

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The p.G406R pathogenic mutation (also known as c.1216G>A), located in coding exon 8A of the CACNA1C gene, results from a G to A substitution at nucleotide position 1216. The glycine at codon 406 is replaced by arginine, an amino acid with dissimilar properties. This mutation has been detected in numerous individuals with Timothy syndrome (TS), including de novo cases and those due to parental mosaicism; incomplete TS has been described in some cases of somatic mosaicism with this mutation (Splawski I et al. Cell, 2004 Oct;119:19-31; Etheridge SP et al. Am. J. Med. Genet. A, 2011 Oct;155A:2578-83; An HS et al. J. Korean Med. Sci., 2013 May;28:788-91;Dufendach KA et al. Pediatrics, 2013 Jun;131:e1991-5; Walsh MA et al. Europace, 2018 02;20:377-385). Functional studies demonstrated altered gating kinetics and prolonged action potential duration, while mouse models with this mutation showed neurobehavioral and brain changes consistent with TS clinical findings (Splawski I et al. Cell, 2004 Oct;119:19-31; Bader PL et al. Proc. Natl. Acad. Sci. U.S.A., 2011 Sep;108:15432-7; Krey JF et al. Nat. Neurosci., 2013 Feb;16:201-9). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. -

Congenital long QT syndrome

Other:1

Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

This variant has been reported in the following publications (PMID:15454078;PMID:15863612;PMID:17224476;PMID:19074970;PMID:21878566). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

CardioboostArm

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.54

BayesDel_noAF

Pathogenic

0.54

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.68

D;.;.;.;.;.;.;.;.;.;.;.;.;.;.;T;.;.

Eigen

Pathogenic

1.0

Eigen_PC

Pathogenic

0.95

FATHMM_MKL

Pathogenic

1.0

M_CAP

Pathogenic

0.80

MetaRNN

Pathogenic

0.94

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Pathogenic

1.1

MutationAssessor

Pathogenic

3.3

.;M;.;M;M;M;M;M;M;M;M;M;M;M;M;.;M;M

PhyloP100

PrimateAI

Pathogenic

0.96

PROVEAN

Pathogenic

-6.8

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

REVEL

Pathogenic

0.96

Sift

Uncertain

0.0050

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.023

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

Polyphen

1.0, 0.96

.;D;.;D;D;D;D;D;D;D;D;D;D;D;D;.;D;D

Vest4

0.95

MutPred

0.71

Loss of ubiquitination at K410 (P = 0.0816);Loss of ubiquitination at K410 (P = 0.0816);Loss of ubiquitination at K410 (P = 0.0816);Loss of ubiquitination at K410 (P = 0.0816);Loss of ubiquitination at K410 (P = 0.0816);Loss of ubiquitination at K410 (P = 0.0816);Loss of ubiquitination at K410 (P = 0.0816);Loss of ubiquitination at K410 (P = 0.0816);Loss of ubiquitination at K410 (P = 0.0816);Loss of ubiquitination at K410 (P = 0.0816);Loss of ubiquitination at K410 (P = 0.0816);Loss of ubiquitination at K410 (P = 0.0816);Loss of ubiquitination at K410 (P = 0.0816);Loss of ubiquitination at K410 (P = 0.0816);Loss of ubiquitination at K410 (P = 0.0816);Loss of ubiquitination at K410 (P = 0.0816);Loss of ubiquitination at K410 (P = 0.0816);Loss of ubiquitination at K410 (P = 0.0816);

MVP

0.99

MPC

2.4

ClinPred

1.0

GERP RS

5.3

gMVP

0.99

Mutation Taster

=0/100

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.97

dbscSNV1_RF

Benign

0.67

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over