Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000520971 | SCV000621670 | uncertain significance | not provided | 2017-10-13 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the DSE gene. The R723Q variant has not been published as pathogenic or been reported as benign to our knowledge. The R723Q variant is not observed in 29/126108 (0.02%) alleles of individuals of Non-Finnish European descent in large population cohorts (Lek et al., 2016). The R723Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. However, this substitution occurs at a position that is not conserved across species, Q723 is wild-type in multiple species, and in silico analysis predicts this variant likely does not alter the protein structure/function |
Invitae | RCV001853691 | SCV002312943 | uncertain significance | Ehlers-Danlos syndrome, musculocontractural type 2 | 2022-07-05 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 723 of the DSE protein (p.Arg723Gln). This variant is present in population databases (rs371043332, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with DSE-related conditions. ClinVar contains an entry for this variant (Variation ID: 452829). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. |
Revvity Omics, |
RCV001853691 | SCV003829126 | uncertain significance | Ehlers-Danlos syndrome, musculocontractural type 2 | 2020-04-29 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV004023623 | SCV004859415 | likely benign | Inborn genetic diseases | 2021-12-07 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |