ClinVar Miner

Submissions for variant NM_015702.3(MMADHC):c.737A>G (p.Asp246Gly)

dbSNP: rs1408840913
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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 RCV001041753 SCV001205388 uncertain significance Methylmalonic aciduria and homocystinuria type cblD 2021-07-14 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glycine at codon 246 of the MMADHC protein (p.Asp246Gly). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with cobalamin D deficiency (PMID: 19058814, 22156578). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). Experimental studies have shown that this missense change affects MMADHC protein function (PMID: 22156578). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
Baylor Genetics RCV001041753 SCV004193227 likely pathogenic Methylmalonic aciduria and homocystinuria type cblD 2023-12-13 criteria provided, single submitter clinical testing

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