Submissions for variant NM_000551.4(VHL):c.164_171dup (p.Arg60fs)

dbSNP: rs886041345

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000267121	SCV000329835	pathogenic	not provided	2018-03-30	criteria provided, single submitter	clinical testing	The c.164_171dupAGGCCGGG variant in the VHL gene has been reported previously in associationwith von Hippel-Lindau syndrome (Chacon-Camacho et al., 2014). The duplication causes aframeshift starting with codon Arginine 60, changes this amino acid to a Glycine residue and creates apremature Stop codon at position 10 of the new reading frame, denoted p.Arg60GlyfsX10. Thisvariant is predicted to cause loss of normal protein function either through protein truncation ornonsense-mediated mRNA decay. Based on the currently available information, we considerc.164_171dupAGGCCGGG to be pathogenic.
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000767231	SCV000897774	pathogenic	Von Hippel-Lindau syndrome	2018-08-01	criteria provided, single submitter	clinical testing
Invitae	RCV001859534	SCV002238441	pathogenic	Chuvash polycythemia; Von Hippel-Lindau syndrome	2023-07-10	criteria provided, single submitter	clinical testing	This premature translational stop signal has been observed in individual(s) with von Hippel-Lindau syndrome (PMID: 24779271). This sequence change creates a premature translational stop signal (p.Arg60Glyfs*10) 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). This variant is not present in population databases (gnomAD no frequency). This variant is also known as c.161_168dupGGAGGCCG. ClinVar contains an entry for this variant (Variation ID: 280053). For these reasons, this variant has been classified as Pathogenic.