Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001229965 | SCV001402429 | uncertain significance | Methylmalonic aciduria and homocystinuria type cblD | 2019-10-02 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with MMADHC-related conditions. This sequence change replaces serine with cysteine at codon 255 of the MMADHC protein (p.Ser255Cys). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and cysteine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15". The cysteine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |