Submissions for variant NM_022336.4(EDAR):c.1284T>G (p.Cys428Trp)

dbSNP: rs886041005

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000481594	SCV000571539	likely pathogenic	not provided	2024-09-24	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); Missense variants in this gene are a common cause of disease and they are underrepresented in the general population; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 31245878, 11035039, 20301291)
Labcorp Genetics (formerly Invitae), Labcorp	RCV003766702	SCV004609695	uncertain significance	Ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant; Autosomal recessive hypohidrotic ectodermal dysplasia syndrome	2023-10-16	criteria provided, single submitter	clinical testing	This sequence change replaces cysteine, which is neutral and slightly polar, with tryptophan, which is neutral and slightly polar, at codon 428 of the EDAR protein (p.Cys428Trp). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with EDAR-related conditions. ClinVar contains an entry for this variant (Variation ID: 422144). 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 EDAR 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.