Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000524493 | SCV000166405 | uncertain significance | Chuvash polycythemia; Von Hippel-Lindau syndrome | 2024-02-01 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 9 of the VHL protein (p.Asp9Asn). This variant is present in population databases (rs587780730, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with VHL-related conditions. ClinVar contains an entry for this variant (Variation ID: 135953). 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 not expected to disrupt VHL protein function with a negative predictive value of 95%. 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. |
Counsyl | RCV000123104 | SCV000488949 | uncertain significance | Von Hippel-Lindau syndrome | 2016-08-05 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001657771 | SCV001874891 | uncertain significance | not provided | 2021-08-25 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as germline pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 22825683) |
Ambry Genetics | RCV002426672 | SCV002743322 | likely benign | Hereditary cancer-predisposing syndrome | 2021-12-06 | 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. |
Revvity Omics, |
RCV001657771 | SCV003820404 | uncertain significance | not provided | 2022-06-16 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV003460872 | SCV004208750 | uncertain significance | Chuvash polycythemia | 2023-08-29 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV000123104 | SCV004815794 | uncertain significance | Von Hippel-Lindau syndrome | 2023-12-13 | criteria provided, single submitter | clinical testing | This missense variant replaces aspartic acid with asparagine at codon 9 of the VHL protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported as a germline variant in individuals affected with VHL-related disorders in the literature. This variant has been identified in 9/172778 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |