Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002234848 | SCV000953423 | uncertain significance | HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED | 2022-05-17 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 264 of the CBS protein (p.Ile264Thr). This variant is present in population databases (rs760212248, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with CBS-related conditions. ClinVar contains an entry for this variant (Variation ID: 656624). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly 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. |
Ambry Genetics | RCV002422802 | SCV002676541 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2019-09-04 | criteria provided, single submitter | clinical testing | The p.I264T variant (also known as c.791T>C), located in coding exon 7 of the CBS gene, results from a T to C substitution at nucleotide position 791. The isoleucine at codon 264 is replaced by threonine, an amino acid with similar properties. In one yeast-growth assay, this variant showed growth similar to the major allele (Dimster-Denk D et al. G3 (Bethesda), 2013 Oct;3:1619-28). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Fulgent Genetics, |
RCV000813085 | SCV002775919 | uncertain significance | Classic homocystinuria | 2021-07-17 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV000813085 | SCV002083789 | uncertain significance | Classic homocystinuria | 2021-04-09 | no assertion criteria provided | clinical testing |