Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001038628 | SCV001202107 | pathogenic | Ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant; Autosomal recessive hypohidrotic ectodermal dysplasia syndrome | 2023-12-30 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 89 of the EDAR protein (p.Arg89His). This variant is present in population databases (rs121908450, gnomAD 0.007%). This missense change has been observed in individual(s) with autosomal recessive hypohidrotic ectodermal dysplasia and/or mild autosomal dominant ectodermal dysplasia (PMID: 18231121, 20236127, 20979233). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 5849). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on EDAR protein function. This variant disrupts the p.Arg89 amino acid residue in EDAR. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
Institute of Human Genetics, |
RCV001253315 | SCV001428969 | pathogenic | Ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant | 2018-01-19 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000006206 | SCV000026388 | pathogenic | Ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, autosomal recessive | 2008-06-01 | no assertion criteria provided | literature only | |
OMIM | RCV000032598 | SCV000056349 | pathogenic | Ectodermal dysplasia 10a, hypohidrotic/hair/tooth type, autosomal dominant | 2008-06-01 | no assertion criteria provided | literature only | |
Hehr Laboratory, |
RCV000681480 | SCV000808930 | pathogenic | Progressive sclerosing poliodystrophy; Mitochondrial DNA depletion syndrome 4b | 2016-10-09 | no assertion criteria provided | clinical testing |