Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002235257 | SCV000769934 | uncertain significance | HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED | 2017-08-17 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine with lysine at codon 250 of the CBS protein (p.Met250Lys). The methionine residue is moderately conserved and there is a moderate physicochemical difference between methionine and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual with elevetaed methionine and homocysteine, findings that are highly specific for homocystinuria (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. |