Submissions for variant NM_001348768.2(HECW2):c.1304C>A (p.Thr435Asn)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003016285	SCV003309375	uncertain significance	not provided	2022-02-11	criteria provided, single submitter	clinical testing	This sequence change replaces threonine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 435 of the HECW2 protein (p.Thr435Asn). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with HECW2-related conditions. 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 HECW2 protein function. 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.
PreventionGenetics, part of Exact Sciences	RCV004741372	SCV005364110	uncertain significance	HECW2-related disorder	2024-03-15	no assertion criteria provided	clinical testing	The HECW2 c.1304C>A variant is predicted to result in the amino acid substitution p.Thr435Asn. To our knowledge, this variant has not been reported in the literature or in a large population database, 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.