Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001062191 | SCV001226973 | uncertain significance | Methylmalonic aciduria and homocystinuria type cblD | 2022-07-15 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 104 of the MMADHC protein (p.Ala104Val). This variant is present in population databases (rs533388008, gnomAD 0.003%). 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: 856679). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. |
Fulgent Genetics, |
RCV001062191 | SCV002791620 | uncertain significance | Methylmalonic aciduria and homocystinuria type cblD | 2021-12-17 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV003160503 | SCV003866932 | uncertain significance | Inborn genetic diseases | 2023-02-28 | criteria provided, single submitter | clinical testing | The c.311C>T (p.A104V) alteration is located in exon 4 (coding exon 3) of the MMADHC gene. This alteration results from a C to T substitution at nucleotide position 311, causing the alanine (A) at amino acid position 104 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Natera, |
RCV001062191 | SCV002083921 | uncertain significance | Methylmalonic aciduria and homocystinuria type cblD | 2020-03-24 | no assertion criteria provided | clinical testing |