Submissions for variant NM_000377.3(WAS):c.989C>T (p.Pro330Leu)

gnomAD frequency: 0.00001  dbSNP: rs1178247738

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001349478	SCV001543823	uncertain significance	X-linked severe congenital neutropenia; Thrombocytopenia 1; Wiskott-Aldrich syndrome	2023-07-26	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 330 of the WAS protein (p.Pro330Leu). 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 WAS protein function. ClinVar contains an entry for this variant (Variation ID: 1045126). This variant has not been reported in the literature in individuals affected with WAS-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.01%).
PreventionGenetics, part of Exact Sciences	RCV003399138	SCV004104345	uncertain significance	WAS-related disorder	2023-08-14	criteria provided, single submitter	clinical testing	The WAS c.989C>T variant is predicted to result in the amino acid substitution p.Pro330Leu. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.