Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000198168 | SCV000249715 | uncertain significance | not provided | 2018-01-03 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the CBS gene. The E451D variant has not been published as pathogenic or been reported as benign to our knowledge. The E451D variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). Nevertheless, the E451D variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Furthermore, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. |
Fulgent Genetics, |
RCV000764259 | SCV000895267 | uncertain significance | Classic homocystinuria | 2021-07-28 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001853129 | SCV002250181 | uncertain significance | HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED | 2021-09-24 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid with aspartic acid at codon 451 of the CBS protein (p.Glu451Asp). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. This variant is present in population databases (rs367962613, ExAC 0.01%). This variant has not been reported in the literature in individuals with CBS-related conditions. ClinVar contains an entry for this variant (Variation ID: 212868). 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, but 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. |
Natera, |
RCV000764259 | SCV001461060 | uncertain significance | Classic homocystinuria | 2020-09-16 | no assertion criteria provided | clinical testing |