ClinVar Miner

Submissions for variant NM_001354723.2(VHL):c.*125C>G (rs28940301)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001219111 SCV001391032 likely pathogenic Erythrocytosis, familial, 2; Von Hippel-Lindau syndrome 2020-06-21 criteria provided, single submitter clinical testing This sequence change replaces histidine with aspartic acid at codon 191 of the VHL protein (p.His191Asp). The histidine residue is moderately conserved and there is a moderate physicochemical difference between histidine and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has been observed as homozygous in individuals affected with erythrocytosis (PMID: 12844285, 23403324, 27651169). In a large family, this variant was observed to segregate with autosomal recessive erythrocytosis in two family members, but clinical features associated with von Hippel-Lindau (VHL) syndrome were not present in family members heterozygous for the variant (PMID: 12844285, 23403324). ClinVar contains an entry for this variant (Variation ID: 2235). This variant has been reported to affect VHL protein function (PMID: 21685897, 23403324). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
OMIM RCV000002323 SCV000022481 pathogenic Erythrocytosis, familial, 2 2011-06-19 no assertion criteria provided literature only

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