ClinVar Miner

Submissions for variant NM_000070.3(CAPN3):c.1657G>A (p.Glu553Lys)

dbSNP: rs767739787
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000668383 SCV000792974 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2A 2017-07-25 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000668383 SCV000935890 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2A 2023-07-26 criteria provided, single submitter clinical testing This variant is present in population databases (rs767739787, gnomAD 0.0009%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 553 of the CAPN3 protein (p.Glu553Lys). This missense change has been observed in individual(s) with autosomal recessive limb-girdle muscular dystrophy type 2A (PMID: 11731278, 15689361, 20044116, 21204801). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 not expected to disrupt CAPN3 protein function. ClinVar contains an entry for this variant (Variation ID: 553020).
Kariminejad - Najmabadi Pathology & Genetics Center RCV001814213 SCV001755277 likely pathogenic Abnormality of the musculature 2021-07-10 criteria provided, single submitter clinical testing
GeneDx RCV001584540 SCV001811560 likely pathogenic not provided 2019-03-22 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 20044116, 15689361, 21204801, 11731278)
Revvity Omics, Revvity RCV001584540 SCV002025063 likely pathogenic not provided 2021-10-07 criteria provided, single submitter clinical testing
Baylor Genetics RCV003459596 SCV004213805 pathogenic Muscular dystrophy, limb-girdle, autosomal dominant 4 2024-03-14 criteria provided, single submitter clinical testing

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