Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000196471 | SCV000250724 | uncertain significance | not provided | 2015-03-02 | criteria provided, single submitter | clinical testing | p.Glu442Gln (GAG>CAG): c.1324 G>C in exon 3 of the SLC2A10 gene (NM_030777.3). A variant of unknown significance has been identified in the SLC2A10 gene. The E442Q variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The E442Q variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The E442Q variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals. Missense mutations in nearby residues (E437K, G445E) have been reported in association with Arterial tortuosity syndrome, supporting the functional importance of this region of the protein. Nevertheless, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. This variant was found in TAADV2-1,TAAD |
Labcorp Genetics |
RCV001037765 | SCV001201195 | uncertain significance | Arterial tortuosity syndrome | 2021-10-09 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid with glutamine at codon 442 of the SLC2A10 protein (p.Glu442Gln). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and glutamine. This variant is present in population databases (rs143265363, ExAC 0.04%). This variant has not been reported in the literature in individuals affected with SLC2A10-related conditions. ClinVar contains an entry for this variant (Variation ID: 213735). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". 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, |
RCV001037765 | SCV003825666 | uncertain significance | Arterial tortuosity syndrome | 2020-10-01 | criteria provided, single submitter | clinical testing |