ClinVar Miner

Submissions for variant NM_000070.3(CAPN3):c.1673C>T (p.Pro558Leu)

gnomAD frequency: 0.00001  dbSNP: rs546820887
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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) RCV000335232 SCV000339516 uncertain significance not provided 2016-02-09 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001859642 SCV002194353 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2A 2025-01-06 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 558 of the CAPN3 protein (p.Pro558Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal recessive CAPN3-related conditions (internal data). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 286185). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt CAPN3 protein function with a positive predictive value of 80%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Revvity Omics, Revvity RCV000335232 SCV003828996 uncertain significance not provided 2021-01-19 criteria provided, single submitter clinical testing
GeneDx RCV000335232 SCV005848863 uncertain significance not provided 2024-08-13 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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