Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000202526 | SCV000822280 | pathogenic | Arterial tortuosity syndrome | 2023-07-08 | criteria provided, single submitter | clinical testing | 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 SLC2A10 protein function. This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 437 of the SLC2A10 protein (p.Glu437Lys). This variant is present in population databases (rs763220502, gnomAD 0.006%). This missense change has been observed in individual(s) with arterial tortuosity syndrome (PMID: 17163528, 17935213, 25373504). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 161100). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV000997785 | SCV001778447 | likely pathogenic | not provided | 2020-09-08 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26376865, 28655553, 17163528, 25373504, 17935213) |
| Center for Genomic Medicine, |
RCV000202526 | SCV004808049 | likely pathogenic | Arterial tortuosity syndrome | 2024-03-29 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000202526 | SCV005062103 | pathogenic | Arterial tortuosity syndrome | 2024-03-08 | criteria provided, single submitter | clinical testing | Variant summary: SLC2A10 c.1309G>A (p.Glu437Lys) results in a conservative amino acid change located in the Major facilitator superfamily domain (IPR020846) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 251422 control chromosomes. c.1309G>A has been reported in the literature in multiple homozygous and compound heterozygous individuals affected with Arterial Tortuosity Syndrome (e.g. Beyens_2018, Callewaert_2008, Drera_2007). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 29323665, 17935213, 17163528). ClinVar contains an entry for this variant (Variation ID: 161100). Based on the evidence outlined above, the variant was classified as pathogenic. |
| Gene |
RCV000202526 | SCV000195654 | not provided | Arterial tortuosity syndrome | no assertion provided | literature only |