ClinVar Miner

Submissions for variant NM_015506.3(MMACHC):c.449T>A (p.Ile150Lys)

dbSNP: rs756413692
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001390451 SCV001592191 pathogenic Cobalamin C disease 2023-01-28 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with lysine, which is basic and polar, at codon 150 of the MMACHC protein (p.Ile150Lys). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Ile150 amino acid residue in MMACHC. Other variant(s) that disrupt this residue have been observed in individuals with MMACHC-related conditions (PMID: 32058304), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 1076507). This missense change has been observed in individual(s) with cobalamin C deficiency (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency).

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