Submissions for variant NM_000551.4(VHL):c.183C>G (p.Pro61=)

gnomAD frequency: 0.00067  dbSNP: rs63650860

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen VHL Variant Curation Expert Panel, ClinGen	RCV000123102	SCV005187309	benign	Von Hippel-Lindau syndrome	2024-06-25	reviewed by expert panel	curation	The variant NM_000551.3(VHL):c.183C>G (p.Pro61=) is a silent variant in the first exon of VHL. The GroupMax Filtering Allele Frequency (95% CI) in gnomAD v4.1.0 is 0.001902 (192/89258 from South Asian Population). This is higher than the ClinGen VHL VCEP threshold of >=0.000156 (0.0156%) threshold expected for VHL disease (BA1) and is classified as Benign for autosomal-dominant von Hippel-Lindau disease (VHL disease) based on the ACMG/AMP criteria applied, as specified by the ClinGen VHL VCEP Version 1.0 (Specifications approval date: 02/26/2024. Variant Approval Date 06/25/2024).
Labcorp Genetics (formerly Invitae), Labcorp	RCV001082042	SCV000166403	benign	Chuvash polycythemia; Von Hippel-Lindau syndrome	2024-01-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000213076	SCV000211837	benign	not specified	2014-09-08	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics	RCV000161102	SCV000213631	likely benign	Hereditary cancer-predisposing syndrome	2014-11-25	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Eurofins Ntd Llc (ga)	RCV000658953	SCV000224255	uncertain significance	not provided	2014-07-29	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000123102	SCV000439635	likely benign	Von Hippel-Lindau syndrome	2018-12-17	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000658953	SCV000605563	benign	not provided	2022-02-04	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000658953	SCV000780756	likely benign	not provided	2024-06-01	criteria provided, single submitter	clinical testing	VHL: BP4, BP7
PreventionGenetics, part of Exact Sciences	RCV000658953	SCV000805323	likely benign	not provided	2018-02-26	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000213076	SCV001467756	benign	not specified	2020-12-03	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000161102	SCV002534147	benign	Hereditary cancer-predisposing syndrome	2020-10-12	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000213076	SCV002760269	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing