ClinVar Miner

Submissions for variant NM_000551.3(VHL):c.344A>G (p.His115Arg) (rs5030812)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000822511 SCV000963318 likely pathogenic Erythrocytosis, familial, 2; Von Hippel-Lindau syndrome 2018-09-13 criteria provided, single submitter clinical testing This sequence change replaces histidine with arginine at codon 115 of the VHL protein (p.His115Arg). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with von Hippel-Lindau syndrome (PMID: 8707293, 22357542). This variant is also known as 557A>G in the literature. Experimental studies have shown that this missense change does not affect the interaction between TBP-1 and VHL, however the clinical significance of this result is uncertain (PMID: 14556007). This variant disrupts the p.His115 amino acid residue in VHL. Other variants that disrupt this residue have been observed in affected individuals (PMID: 9829912, 17024664, 12202531, 7728151, 29749453), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. 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.

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