Submissions for variant NM_019842.4(KCNQ5):c.1076G>A (p.Arg359His)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002294876	SCV002596139	uncertain significance	not provided	2022-10-07	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 expected to disrupt KCNQ5 protein function. This variant has not been reported in the literature in individuals affected with KCNQ5-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 359 of the KCNQ5 protein (p.Arg359His).
Institute of Human Genetics, University of Leipzig Medical Center	RCV003322632	SCV004027682	likely pathogenic	Intellectual disability, autosomal dominant 46	2023-05-24	criteria provided, single submitter	clinical testing	Criteria applied: PM1,PM5,PM2_SUP,PP3