ClinVar Miner

Submissions for variant NM_015506.3(MMACHC):c.643T>C (p.Tyr215His)

dbSNP: rs755843695
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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 RCV001323234 SCV001514142 pathogenic Cobalamin C disease 2023-10-14 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 215 of the MMACHC protein (p.Tyr215His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of 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. ClinVar contains an entry for this variant (Variation ID: 1023220). 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. For these reasons, this variant has been classified as Pathogenic.
Natera, Inc. RCV001323234 SCV002089553 uncertain significance Cobalamin C disease 2018-11-01 no assertion criteria provided clinical testing

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