Submissions for variant NM_000551.4(VHL):c.180del (p.Val62fs)

dbSNP: rs730882037

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000161096	SCV000211831	pathogenic	Hereditary cancer-predisposing syndrome	2014-06-03	criteria provided, single submitter	clinical testing	The c.180delG mutation in the VHL gene has been reported previously (as 393delG) in association with von Hippel-Lindau (VHL) syndrome (Stolle et al., 1998). The deletion causes a frameshift starting with codon Valine 62, changes this amino acid to a Cysteine residue and creates a premature Stop codon at position 5 of the new reading frame, denoted p.Val62CysfsX5. This mutation is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The variant is found in VHL panel(s).
Invitae	RCV003765009	SCV004569648	pathogenic	Chuvash polycythemia; Von Hippel-Lindau syndrome	2023-09-17	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 182986). This variant is also known as 393delG. This premature translational stop signal has been observed in individual(s) with von Hippel-Lindau syndrome (PMID: 7728151). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Val62Cysfs*5) in the VHL gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in VHL are known to be pathogenic (PMID: 8956040, 12202531).