ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.104C>A (p.Ala35Asp)

dbSNP: rs587780536
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000119148 SCV000153867 uncertain significance Chuvash polycythemia; Von Hippel-Lindau syndrome 2024-01-18 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 35 of the VHL protein (p.Ala35Asp). This variant is not present in population databases (gnomAD no frequency). 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: 132707). 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. 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 RCV000663333 SCV000786608 uncertain significance Von Hippel-Lindau syndrome 2018-06-06 criteria provided, single submitter clinical testing
Ambry Genetics RCV001017126 SCV001178158 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-28 criteria provided, single submitter clinical testing The p.A35D variant (also known as c.104C>A), located in coding exon 1 of the VHL gene, results from a C to A substitution at nucleotide position 104. The alanine at codon 35 is replaced by aspartic acid, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV001588931 SCV001814967 uncertain significance not provided 2019-09-25 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Sema4, Sema4 RCV001017126 SCV002534134 uncertain significance Hereditary cancer-predisposing syndrome 2021-10-15 criteria provided, single submitter curation
Baylor Genetics RCV003460840 SCV004208782 uncertain significance Chuvash polycythemia 2023-05-15 criteria provided, single submitter clinical testing

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