Submissions for variant NM_001130987.2(DYSF):c.4078C>G (p.Arg1360Gly)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002664240	SCV003524595	pathogenic	Qualitative or quantitative defects of dysferlin	2022-12-04	criteria provided, single submitter	clinical testing	This variant disrupts the p.Arg1342 amino acid residue in DYSF. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 21522182). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 expected to disrupt DYSF protein function. This missense change has been observed in individual(s) with limb girdle muscular dystrophy type 2B (PMID: 27647186). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 1342 of the DYSF protein (p.Arg1342Gly). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics	RCV003459773	SCV004196501	likely pathogenic	Miyoshi muscular dystrophy 1	2024-03-14	criteria provided, single submitter	clinical testing