NM_000720.4(CACNA1D):c.1127C>T (p.Ala376Val) AND Sinoatrial node dysfunction and deafness

Germline classification:: Likely pathogenic (3 submissions)
Last evaluated:: Aug 1, 2020
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000454162.4

Allele description [Variation Report for NM_000720.4(CACNA1D):c.1127C>T (p.Ala376Val)]

NM_000720.4(CACNA1D):c.1127C>T (p.Ala376Val)

Gene:

CACNA1D:calcium voltage-gated channel subunit alpha1 D [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p21.1

Genomic location:

Preferred name:

NM_000720.4(CACNA1D):c.1127C>T (p.Ala376Val)

Other names:

NM_000720.2:c.1127C>T, p.(Ala376Val)

HGVS:

NC_000003.12:g.53673723C>T
NG_032999.1:g.183675C>T
NM_000720.4:c.1127C>T
NM_001128839.3:c.1220+597C>T
NM_001128840.3:c.1220+597C>TMANE SELECT
NP_000711.1:p.Ala376Val
NC_000003.11:g.53707750C>T
NM_000720.2:c.1127C>T

Protein change:

A376V

Links:

dbSNP: rs759274321

NCBI 1000 Genomes Browser:

rs759274321

Molecular consequence:

NM_001128839.3:c.1220+597C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001128840.3:c.1220+597C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_000720.4:c.1127C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Sinoatrial node dysfunction and deafness (SANDD)
Identifiers:: MONDO: MONDO:0013960; MedGen: C3554018; Orphanet: 324321; OMIM: 614896

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000538131	Hereditary Research Laboratory, Bethlehem University	no assertion criteria provided	Pathogenic (Jun 4, 2016)	germline	research
SCV001480019	University of Washington Center for Mendelian Genomics, University of Washington	no assertion criteria provided	Likely pathogenic	inherited	research	PubMed (1) [See all records that cite this PMID]
SCV001976373	King Laboratory, University of Washington	criteria provided, single submitter (Abu Rayyan A et al. (Proc Natl Acad Sci U S A 2020))	Likely pathogenic (Aug 1, 2020)	germline	research	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000538131

Hereditary Research Laboratory, Bethlehem University

no assertion criteria provided

Pathogenic
(Jun 4, 2016)

germline

research

SCV001480019

University of Washington Center for Mendelian Genomics, University of Washington

no assertion criteria provided

Likely pathogenic

inherited

research

PubMed (1)
[See all records that cite this PMID]

SCV001976373

King Laboratory, University of Washington

criteria provided, single submitter

(Abu Rayyan A et al. (Proc Natl Acad Sci U S A 2020))

Likely pathogenic
(Aug 1, 2020)

germline

research

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	research
not provided	inherited	yes	not provided	not provided	not provided	not provided	not provided	research

Citations

PubMed

Identification of CACNA1D variants associated with sinoatrial node dysfunction and deafness in additional Pakistani families reveals a clinical significance.

Liaqat K, Schrauwen I, Raza SI, Lee K, Hussain S, Chakchouk I, Nasir A, Acharya A, Abbe I, Umair M, Ansar M, Ullah I, Shah K; University of Washington Center for Mendelian Genomics, Bamshad MJ, Nickerson DA, Ahmad W, Leal SM.

J Hum Genet. 2019 Feb;64(2):153-160. doi: 10.1038/s10038-018-0542-8. Epub 2018 Nov 30.

PubMed [citation]

PMID:: 30498240
PMCID:: PMC6561484

Genomic analysis of inherited hearing loss in the Palestinian population.

Abu Rayyan A, Kamal L, Casadei S, Brownstein Z, Zahdeh F, Shahin H, Canavati C, Dweik D, Jaraysa T, Rabie G, Carlson RJ, Gulsuner S, Lee MK, Avraham KB, Walsh T, King MC, Kanaan MN.

Proc Natl Acad Sci U S A. 2020 Aug 18;117(33):20070-20076. doi: 10.1073/pnas.2009628117. Epub 2020 Aug 3.

PubMed [citation]

PMID:: 32747562
PMCID:: PMC7443947

Details of each submission

From Hereditary Research Laboratory, Bethlehem University, SCV000538131.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	not provided

Description

congenital, moderate

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From University of Washington Center for Mendelian Genomics, University of Washington, SCV001480019.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	inherited	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From King Laboratory, University of Washington, SCV001976373.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (1)

Description

CACNA1D c.1127C>T, p.A376V alters a completely conserved residue in a transmembrane domain of CACNA1D. The variant is homozygous in 6 children from 4 Palestinian families with a syndromic phenotype including moderate pre-lingual hearing loss and cardiac signs (Abu Rayyan 2020). It is absent from 1300 Palestinian controls and present in 4/251488 alleles on gnomAD, all in heterozygotes.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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