ClinVar Miner

Submissions for variant NM_000254.3(MTR):c.1348_1349inv (p.Ser450Asp)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001900684 SCV002142028 pathogenic Methylcobalamin deficiency type cblG 2023-12-21 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 450 of the MTR protein (p.Ser450Asp). This variant is present in population databases (no rsID available, gnomAD 0.002%). This missense change has been observed in individual(s) with cobalamin G deficiency (PMID: 30041674; 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: 1374754). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant disrupts the p.Ser450 amino acid residue in MTR. Other variant(s) that disrupt this residue have been observed in individuals with MTR-related conditions (PMID: 12068375, 20490923), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV002482600 SCV002790783 uncertain significance Methylcobalamin deficiency type cblG; Neural tube defects, folate-sensitive 2022-02-10 criteria provided, single submitter clinical testing

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