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

dbSNP: rs367543049

Total submissions: 3

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	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. For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 42106). 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. This variant is not present in population databases (gnomAD no frequency). 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).
Clinical Genetics Laboratory, Skane University Hospital Lund	RCV005234924	SCV005882884	pathogenic	Congenital myopathy	2024-08-12	criteria provided, single submitter	clinical testing	PS2, PS4, PM2, PP3
GeneReviews	RCV000034933	SCV000058541	not provided	Congenital myopathy with fiber type disproportion		no assertion provided	literature only