Reclassification of the p.Ile208Val variant by case-level data sharing.

Cold Spring Harb Mol Case Stud
Authors
Keywords
Abstract

The ClinVar database is a useful tool for patients and physicians to view variant interpretations submitted by clinical and nonclinical labs. However, variants of uncertain significance (VUS) in ClinVar can pose a significant burden on patients. If possible, it is important to resolve discrepancies and uncertainties surrounding interpreted variants. Here we highlight a case of a family who received a report of a variant (c.622A>G, p.Ile208Val) in following prenatal RASopathy testing. The variant had been previously classified by our laboratory as a VUS, so the mother contacted our laboratory via ClinVar for further information, which prompted reevaluation of the variant. Multiple sources of case-level data as well as the presence of the variant in the general population yielded sufficient evidence to reclassify the variant as likely benign. This reclassification alleviated significant concern for the family, and the child was born healthy with no clinical manifestations of Noonan syndrome or a RASopathy.

Year of Publication
2018
Journal
Cold Spring Harb Mol Case Stud
Volume
4
Issue
5
Date Published
2018 10
ISSN
2373-2873
DOI
10.1101/mcs.a002675
PubMed ID
29945942
PubMed Central ID
PMC6169827
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