Submissions for variant NM_005343.4(HRAS):c.503T>C (p.Leu168Pro)

dbSNP: rs756367459

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001203653	SCV001374827	uncertain significance	Costello syndrome	2019-06-25	criteria provided, single submitter	clinical testing	This sequence change replaces leucine with proline at codon 168 of the HRAS protein (p.Leu168Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is present in population databases (rs756367459, ExAC 0.002%). This variant has not been reported in the literature in individuals with HRAS-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001813581	SCV002060767	uncertain significance	Noonan syndrome and Noonan-related syndrome	2020-11-16	criteria provided, single submitter	clinical testing
Clinical Genetics Laboratory, Skane University Hospital Lund	RCV004697069	SCV005198444	uncertain significance	not provided	2023-09-25	criteria provided, single submitter	clinical testing