ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.274G>T (p.Asp92Tyr)

gnomAD frequency: 0.00003  dbSNP: rs587780731
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000123105 SCV000166406 uncertain significance Chuvash polycythemia; Von Hippel-Lindau syndrome 2023-07-07 criteria provided, single submitter clinical testing 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on VHL protein function. ClinVar contains an entry for this variant (Variation ID: 135954). This variant has not been reported in the literature in individuals affected with VHL-related conditions. This variant is present in population databases (rs587780731, gnomAD 0.03%). This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 92 of the VHL protein (p.Asp92Tyr).
Ambry Genetics RCV001016495 SCV001177455 likely benign Hereditary cancer-predisposing syndrome 2024-02-20 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.
Sema4, Sema4 RCV001016495 SCV002534153 uncertain significance Hereditary cancer-predisposing syndrome 2022-03-02 criteria provided, single submitter curation

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