ClinVar Miner

Submissions for variant NM_000254.3(MTR):c.2020C>T (p.Arg674Cys)

gnomAD frequency: 0.00001  dbSNP: rs150058137
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein RCV002253108 SCV002523262 uncertain significance See cases 2019-09-30 criteria provided, single submitter clinical testing ACMG classification criteria: PM2
Labcorp Genetics (formerly Invitae), Labcorp RCV003774744 SCV004651377 pathogenic Methylcobalamin deficiency type cblG 2024-03-14 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 674 of the MTR protein (p.Arg674Cys). This variant is present in population databases (rs150058137, gnomAD 0.008%). This missense change has been observed in individual(s) with cobalamin G deficiency (Invitae). ClinVar contains an entry for this variant (Variation ID: 1690690). 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 MTR protein function with a positive predictive value of 80%. This variant disrupts the p.Arg674 amino acid residue in MTR. Other variant(s) that disrupt this residue have been observed in individuals with MTR-related conditions (PMID: 25526710), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.

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