Submissions for variant NM_004006.3(DMD):c.824C>A (p.Ser275Tyr)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003511580	SCV004309184	uncertain significance	Duchenne muscular dystrophy	2023-12-22	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 275 of the DMD protein (p.Ser275Tyr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DMD-related conditions. 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 DMD protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics	RCV004992669	SCV005566474	uncertain significance	Cardiovascular phenotype	2024-06-29	criteria provided, single submitter	clinical testing	The p.S275Y variant (also known as c.824C>A), located in coding exon 8 of the DMD gene, results from a C to A substitution at nucleotide position 824. The serine at codon 275 is replaced by tyrosine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.