ClinVar Miner

Submissions for variant NM_015702.3(MMADHC):c.557T>C (p.Met186Thr)

gnomAD frequency: 0.00029  dbSNP: rs61755260
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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 RCV001239948 SCV001412857 uncertain significance Methylmalonic aciduria and homocystinuria type cblD 2024-11-05 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 186 of the MMADHC protein (p.Met186Thr). This variant is present in population databases (rs61755260, gnomAD 0.1%). 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: 965486). 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.
Revvity Omics, Revvity RCV001239948 SCV003808858 uncertain significance Methylmalonic aciduria and homocystinuria type cblD 2022-04-18 criteria provided, single submitter clinical testing
Ambry Genetics RCV004034632 SCV005008721 uncertain significance Inborn genetic diseases 2022-04-22 criteria provided, single submitter clinical testing The c.557T>C (p.M186T) alteration is located in exon 6 (coding exon 5) of the MMADHC gene. This alteration results from a T to C substitution at nucleotide position 557, causing the methionine (M) at amino acid position 186 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001239948 SCV002083917 uncertain significance Methylmalonic aciduria and homocystinuria type cblD 2020-02-13 no assertion criteria provided clinical testing

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