ClinVar Miner

Submissions for variant NM_000070.3(CAPN3):c.2219G>A (p.Gly740Asp)

gnomAD frequency: 0.00001  dbSNP: rs750162858
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000594969 SCV000704199 uncertain significance not provided 2016-12-07 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001270825 SCV001451589 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2A 2020-06-04 criteria provided, single submitter clinical testing The CAPN3 c.2219G>A (p.Gly740Asp) variant is a missense variant. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. The variant is reported at a frequency of 0.000018 in the European (non-Finnish) population from the Genome Aggregation Database though this is based on two alleles in a region of good sequencing coverage, so the variant is presumed to be rare. Based on the limited evidence, the p.Gly740Asp variant is classified as a variant of uncertain significance for calpainopathy.
Labcorp Genetics (formerly Invitae), Labcorp RCV001270825 SCV002142238 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2A 2022-09-05 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 740 of the CAPN3 protein (p.Gly740Asp). This variant is present in population databases (rs750162858, gnomAD 0.0009%). This missense change has been observed in individual(s) with limb-girdle muscular dystrophy (PMID: 30564623). ClinVar contains an entry for this variant (Variation ID: 498936). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CAPN3 protein function. 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.
Revvity Omics, Revvity RCV000594969 SCV003828968 uncertain significance not provided 2019-12-09 criteria provided, single submitter clinical testing

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