ClinVar Miner

Submissions for variant NM_015702.3(MMADHC):c.136G>C (p.Ala46Pro)

dbSNP: rs749521854
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000986829 SCV001135968 uncertain significance Methylmalonic aciduria and homocystinuria type cblD 2019-05-28 criteria provided, single submitter clinical testing
Invitae RCV000986829 SCV003505094 uncertain significance Methylmalonic aciduria and homocystinuria type cblD 2022-06-26 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 46 of the MMADHC protein (p.Ala46Pro). This variant is present in population databases (rs749521854, gnomAD no frequency). 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: 801761). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The proline amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein RCV000986829 SCV003807972 uncertain significance Methylmalonic aciduria and homocystinuria type cblD 2022-11-19 criteria provided, single submitter clinical testing ACMG classification criteria: PM2 moderated, BP4 supporting

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