ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.532C>G (p.Leu178Val)

dbSNP: rs755146587
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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 RCV000694261 SCV000822697 uncertain significance Chuvash polycythemia; Von Hippel-Lindau syndrome 2022-08-17 criteria provided, single submitter clinical testing This variant is present in population databases (rs755146587, gnomAD 0.0009%). 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. This variant disrupts the p.Leu178 amino acid residue in VHL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7987306, 17024664, 19464396, 19763184, 27527340). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 VHL protein function. ClinVar contains an entry for this variant (Variation ID: 572788). This variant has not been reported in the literature in individuals affected with VHL-related conditions. This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 178 of the VHL protein (p.Leu178Val).
Ambry Genetics RCV003303142 SCV004006353 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-10 criteria provided, single submitter clinical testing The p.L178V variant (also known as c.532C>G), located in coding exon 3 of the VHL gene, results from a C to G substitution at nucleotide position 532. The leucine at codon 178 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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