ClinVar Miner

Submissions for variant NM_000551.3(VHL):c.123_137del (p.38_42SGPEE[1]) (rs863224839)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000222096 SCV000276096 uncertain significance Hereditary cancer-predisposing syndrome 2018-02-14 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Rarity in general population databases (dbsnp, esp, 1000 genomes),Insufficient evidence
GeneDx RCV000255039 SCV000322352 uncertain significance not provided 2018-06-18 criteria provided, single submitter clinical testing This in-frame deletion of 15 nucleotides in VHL is denoted c.123_137del15 at the cDNA level and p.Ser43_Glu47del (S43_E47del) at the protein level. The normal sequence, with the bases that are deleted in brackets, is CGGA[del15]GGAA. This variant has been observed in one family enrolled in the French VHL Registry (Gallou 2004). VHL Ser43_Glu47del was not observed in large population cohorts (Lek 2016). This deletion is located within repeat regions 6 and 7 (UniProt). In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Since in-frame deletions may or may not inhibit proper protein functioning, the clinical significance of this finding remains unclear at this time and we consider VHL Ser43_Glu47del to be a variant of uncertain significance.
Invitae RCV000197814 SCV000255297 uncertain significance Erythrocytosis, familial, 2; Von Hippel-Lindau syndrome 2018-12-05 criteria provided, single submitter clinical testing This variant, c.123_137del, results in the deletion of 5 amino acids of the VHL protein (p.Ser43_Glu47del), but otherwise preserves the integrity of the reading frame. While this variant is present in population databases (rs758049121), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been reported in an individual affected with von Hippel-Lindau (VHL) disease (PMID: 15300849), but it was incorrectly stated as a frameshift mutation. ClinVar contains an entry for this variant (Variation ID: 216870). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acids is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.