Total submissions: 3
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, |
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 |