ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.40G>C (p.Gly14Arg)

gnomAD frequency: 0.00001  dbSNP: rs1060503559
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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 RCV000467814 SCV000553398 uncertain significance Chuvash polycythemia; Von Hippel-Lindau syndrome 2022-02-26 criteria provided, single submitter clinical testing 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. ClinVar contains an entry for this variant (Variation ID: 411969). This variant has not been reported in the literature in individuals affected with VHL-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 14 of the VHL protein (p.Gly14Arg). 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.
Fulgent Genetics, Fulgent Genetics RCV002475889 SCV002787453 uncertain significance Chuvash polycythemia; Pheochromocytoma; Von Hippel-Lindau syndrome; Nonpapillary renal cell carcinoma 2021-12-18 criteria provided, single submitter clinical testing
Ambry Genetics RCV003168862 SCV003885802 uncertain significance Hereditary cancer-predisposing syndrome 2022-11-23 criteria provided, single submitter clinical testing The p.G14R variant (also known as c.40G>C), located in coding exon 1 of the VHL gene, results from a G to C substitution at nucleotide position 40. The glycine at codon 14 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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