Submissions for variant NM_000254.3(MTR):c.118A>G (p.Met40Val)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV003329030	SCV004035790	uncertain significance	not provided	2023-03-14	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); 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
Labcorp Genetics (formerly Invitae), Labcorp	RCV005103917	SCV005832804	uncertain significance	Methylcobalamin deficiency type cblG	2024-10-07	criteria provided, single submitter	clinical testing	This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 40 of the MTR protein (p.Met40Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MTR-related conditions. ClinVar contains an entry for this variant (Variation ID: 2580055). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MTR protein function. 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.