Submissions for variant NM_000429.3(MAT1A):c.829C>T (p.His277Tyr)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002609747	SCV002962246	likely pathogenic	Hepatic methionine adenosyltransferase deficiency	2023-02-25	criteria provided, single submitter	clinical testing	This missense change has been observed in individual(s) with autosomal recessive hypermethioninemia (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1927181). 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 MAT1A protein function. 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. This variant is present in population databases (rs771536750, gnomAD 0.005%). This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 277 of the MAT1A protein (p.His277Tyr).
GeneDx	RCV004765544	SCV005376022	uncertain significance	not provided	2023-12-08	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge