Submissions for variant NM_005343.4(HRAS):c.548G>A (p.Ser183Asn)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001037216	SCV001200617	uncertain significance	Costello syndrome	2023-03-17	criteria provided, single submitter	clinical testing	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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt HRAS protein function. ClinVar contains an entry for this variant (Variation ID: 836160). This variant has not been reported in the literature in individuals affected with HRAS-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 183 of the HRAS protein (p.Ser183Asn).
Service de Génétique Moléculaire, Hôpital Robert Debré	RCV001261055	SCV001438457	likely benign	Noonan syndrome		no assertion criteria provided	clinical testing