Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002517169 | SCV000649825 | uncertain significance | HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED | 2022-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 425 of the CBS protein (p.Val425Met). This variant is present in population databases (rs138211175, gnomAD 0.2%). 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: 212866). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CBS protein function. 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. |
| Eurofins Ntd Llc |
RCV000592999 | SCV000707986 | uncertain significance | not provided | 2017-04-24 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002315524 | SCV000738474 | likely benign | Familial thoracic aortic aneurysm and aortic dissection | 2022-05-04 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| ARUP Laboratories, |
RCV000592999 | SCV001472077 | uncertain significance | not provided | 2019-08-01 | criteria provided, single submitter | clinical testing | The CBS c.1273G>A; p.Val425Met variant (rs138211175), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 212866). This variant is found in the African population with an allele frequency of 0.15% (30/20090 alleles) in the Genome Aggregation Database. The valine at codon 425 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Due to limited information, the clinical significance of the p.Val425Met variant is uncertain at this time. |
| Natera, |
RCV000554628 | SCV002083770 | uncertain significance | Classic homocystinuria | 2020-02-21 | no assertion criteria provided | clinical testing |