Submissions for variant NM_000551.4(VHL):c.463+8C>T (rs5030834)

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000115747	SCV000149656	likely benign	not specified	2017-11-01	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.
Invitae	RCV001084968	SCV000166410	benign	Erythrocytosis, familial, 2; Von Hippel-Lindau syndrome	2019-12-31	criteria provided, single submitter	clinical testing
Vantari Genetics	RCV000210772	SCV000267099	likely benign	Hereditary cancer-predisposing syndrome	2016-02-05	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine	RCV000115747	SCV000540656	likely benign	not specified	2016-03-28	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Outside splice consensus; 2 pubs in HGMD describe 1 proband with no segs
Integrated Genetics/Laboratory Corporation of America	RCV000589592	SCV000697517	benign	not provided	2016-01-13	criteria provided, single submitter	clinical testing	Variant summary: Variant of interest is a substitution of a non-conserved nucleotide located at an intronic position not widely known to affect splicing. 5/5 in silico tools via Alamut predict no impact on normal splicing by the variant along with mutation taster predicting a neutral outcome. The variant was found in the European and African subcohorts of the ExAC project at an allele frequency of 0.076% and 0.048% respectively. These allele frequencies exceed the maximal expected allele frequency of a disease causing VHL variant (0.0028%) indicating the variant to be non-disease causing. It was also seen in patients with phaeochromocytoma, suspected VHL disease and with sporadic RCC, however without strong evidence for pathogenicity. Multiple clinical diagnostic laboratories classify variant as Likely Benign/Benign via ClinVar (without evidence to independently evaluate). Considering the high prevalence of the variant in the general population this variant is classified as benign.
Counsyl	RCV000123108	SCV000785566	likely benign	Von Hippel-Lindau syndrome	2017-09-20	criteria provided, single submitter	clinical testing
PreventionGenetics,PreventionGenetics	RCV000589592	SCV000805351	likely benign	not provided	2017-02-17	criteria provided, single submitter	clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen	RCV000589592	SCV001153780	uncertain significance	not provided	2018-10-01	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000123108	SCV001304545	uncertain significance	Von Hippel-Lindau syndrome	2018-08-08	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. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia	RCV000123108	SCV000264746	likely benign	Von Hippel-Lindau syndrome	2016-02-26	no assertion criteria provided	clinical testing