Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002389708 | SCV002701974 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2018-05-14 | criteria provided, single submitter | clinical testing | The p.D35Y variant (also known as c.103G>T), located in coding exon 1 of the CBS gene, results from a G to T substitution at nucleotide position 103. The aspartic acid at codon 35 is replaced by tyrosine, an amino acid with highly dissimilar properties. In one study, a different alteration located at the same position, p.D35Q (c.103G>A), was detected in an individual with non B6 responsive homocystinuria. This alteration was confirmed to be in cis with CBS p.W43* (c.129G>A) and in trans with p.H232D (c.694C>G) in this individual (Katsushima F et al. Mol. Genet. Metab., 2006 Apr;87:323-8). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV003095232 | SCV003245227 | uncertain significance | HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED | 2022-05-17 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 35 of the CBS protein (p.Asp35Tyr). This variant is present in population databases (rs368471318, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with CBS-related conditions. 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: "Benign"; 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. |