ClinVar Miner

Submissions for variant NM_015506.3(MMACHC):c.795_*18delinsGTATGGTA (p.Ala266fs)

dbSNP: rs1643689610
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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 RCV001217288 SCV001389122 uncertain significance Cobalamin C disease 2022-01-15 criteria provided, single submitter clinical testing This sequence change results in a frameshift in the MMACHC gene (p.Ala266Tyrfs*22). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 17 amino acid(s) of the MMACHC protein and extend the protein by 4 additional amino acid residues. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MMACHC-related conditions. ClinVar contains an entry for this variant (Variation ID: 946424). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant disrupts a region of the MMACHC protein in which other variant(s) (p.Arg267Gln) have been observed in individuals with MMACHC-related conditions (PMID: 24126030). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. 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.

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