ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.413C>T (p.Pro138Leu)

gnomAD frequency: 0.00001  dbSNP: rs780178275
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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 RCV001064218 SCV001229104 uncertain significance Chuvash polycythemia; Von Hippel-Lindau syndrome 2022-11-18 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. Experimental studies have shown that this missense change affects VHL function (PMID: 29891534). 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: 816689). This missense change has been observed in individual(s) with congenital polycythemia (PMID: 23538339). This variant is present in population databases (rs780178275, gnomAD 0.006%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 138 of the VHL protein (p.Pro138Leu).
GeneDx RCV001759686 SCV001986076 uncertain significance not provided 2019-08-20 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 26224408, 24729484, 23538339, 24115288, 29891534)
OMIM RCV001007630 SCV001167318 pathogenic Chuvash polycythemia 2011-07-01 no assertion criteria provided literature only

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