ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.104C>T (p.Ala35Val)

dbSNP: rs587780536
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000631275 SCV000752303 uncertain significance Chuvash polycythemia; Von Hippel-Lindau syndrome 2023-10-10 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 35 of the VHL protein (p.Ala35Val). This variant is present in population databases (no rsID available, gnomAD 0.004%). 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: 526678). 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.
Ambry Genetics RCV003343961 SCV004066598 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-15 criteria provided, single submitter clinical testing The p.A35V variant (also known as c.104C>T), located in coding exon 1 of the VHL gene, results from a C to T substitution at nucleotide position 104. The alanine at codon 35 is replaced by valine, an amino acid with similar properties. This amino acid position is 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.

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