Submissions for variant NM_000551.4(VHL):c.444del (p.Phe148fs)

dbSNP: rs869025653

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001387330	SCV001587933	pathogenic	Chuvash polycythemia; Von Hippel-Lindau syndrome	2020-06-29	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the VHL protein. Other variant(s) that disrupt this region (p.Ser183*) have been determined to be pathogenic (PMID: 8707293, 10567493, 11309459). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This variant has been reported in individual(s) with clinical features of von Hippel-Lindau syndrome (PMID: 8641695). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 223212). This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the VHL gene (p.Phe148Leufs*11). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 66 amino acids of the VHL protein.
Myriad Genetics, Inc.	RCV000208793	SCV004185955	pathogenic	Von Hippel-Lindau syndrome	2023-10-09	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000208793	SCV000264738	pathogenic	Von Hippel-Lindau syndrome	2016-02-26	no assertion criteria provided	clinical testing