ClinVar Miner

Submissions for variant NM_001100.4(ACTA1):c.143G>A (p.Gly48Asp)

dbSNP: rs367543049
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000807360 SCV000947408 pathogenic Actin accumulation myopathy 2022-07-18 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 48 of the ACTA1 protein (p.Gly48Asp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with congenital myopathy and/or autosomal dominant congenital fiber type disproportion (PMID: 19562689, 21520333, 27447704). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 42106). 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 ACTA1 protein function. This variant disrupts the p.Gly48 amino acid residue in ACTA1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 19562689, 24642510, 26172852). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
GeneReviews RCV000034933 SCV000058541 not provided Congenital myopathy with fiber type disproportion no assertion provided literature only

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