ClinVar Miner

Submissions for variant NM_015702.3(MMADHC):c.41A>G (p.Tyr14Cys)

gnomAD frequency: 0.00001  dbSNP: rs756550492
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000805239 SCV000945187 uncertain significance Methylmalonic aciduria and homocystinuria type cblD 2024-09-05 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 14 of the MMADHC protein (p.Tyr14Cys). This variant is present in population databases (rs756550492, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with MMADHC-related conditions. ClinVar contains an entry for this variant (Variation ID: 650141). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt MMADHC protein function with a positive predictive value of 80%. 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.
GeneDx RCV003442088 SCV004169870 uncertain significance not provided 2023-05-04 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Breakthrough Genomics, Breakthrough Genomics RCV003442088 SCV005187930 uncertain significance not provided criteria provided, single submitter not provided
Natera, Inc. RCV000805239 SCV002083923 uncertain significance Methylmalonic aciduria and homocystinuria type cblD 2021-06-22 no assertion criteria provided clinical testing

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