ClinVar Miner

Submissions for variant NM_001128840.3(CACNA1D):c.1220+597C>T

gnomAD frequency: 0.00004  dbSNP: rs759274321
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
King Laboratory,University of Washington RCV000454162 SCV001976373 likely pathogenic Sinoatrial node dysfunction and deafness 2020-08-01 criteria provided, single submitter research 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.
Invitae RCV001861652 SCV002220630 uncertain significance not provided 2021-10-26 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 376 of the CACNA1D protein (p.Ala376Val). This variant is present in population databases (rs759274321, gnomAD 0.01%). This missense change has been observed in individual(s) with autosomal recessive deafness and/or sinoatrial node dysfunction (PMID: 30498240, 32747562). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 402284). 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 C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Hereditary Research Laboratory, Bethlehem University RCV000454162 SCV000538131 pathogenic Sinoatrial node dysfunction and deafness 2016-06-04 no assertion criteria provided research congenital, moderate
University of Washington Center for Mendelian Genomics, University of Washington RCV000454162 SCV001480019 likely pathogenic Sinoatrial node dysfunction and deafness no assertion criteria provided research

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