ClinVar Miner

Submissions for variant NM_015506.3(MMACHC):c.481C>G (p.Arg161Gly)

dbSNP: rs370596113
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV001004154 SCV001162912 likely pathogenic Cobalamin C disease criteria provided, single submitter clinical testing
Invitae RCV001004154 SCV002215172 pathogenic Cobalamin C disease 2023-10-13 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 161 of the MMACHC protein (p.Arg161Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with cobalamin C deficiency (PMID: 16311595). 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: 813351). 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) has been performed at Invitae 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 MMACHC protein function. Experimental studies have shown that this missense change affects MMACHC function (PMID: 25809485, 32457044). This variant disrupts the p.Arg161 amino acid residue in MMACHC. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16311595, 17853453, 19370762, 19700356, 20219402, 21055272, 22560872, 25687216, 25809485, 26283149, 28218226). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV001004154 SCV002786890 pathogenic Cobalamin C disease 2022-04-19 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001004154 SCV004178184 likely pathogenic Cobalamin C disease 2023-04-11 criteria provided, single submitter clinical testing

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