Submissions for variant NM_000255.4(MMUT):c.277C>T (p.Arg93Cys)

gnomAD frequency: 0.00006  dbSNP: rs746274670

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV001815368	SCV002062680	likely pathogenic	not provided	2021-11-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001815368	SCV003439439	likely pathogenic	not provided	2024-05-20	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 93 of the MUT protein (p.Arg93Cys). This variant is present in population databases (rs746274670, gnomAD 0.007%). This missense change has been observed in individual(s) with methylmalonic aciduria (PMID: 26270765, 36717752). ClinVar contains an entry for this variant (Variation ID: 553695). 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 MUT protein function with a positive predictive value of 95%. This variant disrupts the p.Arg93 amino acid residue in MUT. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 1670635, 16281286, 16490061). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Counsyl	RCV000669202	SCV000793931	uncertain significance	Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency	2017-09-12	flagged submission	clinical testing
Myelin Disorders Clinic-Children's Medical Center/Medical Genetics Lab-Tarbiat Modares University, Children's Medical Center, Pediatrics Center of Excellence,	RCV000669202	SCV001245436	uncertain significance	Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency		no assertion criteria provided	clinical testing