ClinVar Miner

Submissions for variant NM_030777.4(SLC2A10):c.1276G>T (p.Gly426Trp) (rs121908172)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000199687 SCV000250723 pathogenic not provided 2014-06-03 criteria provided, single submitter clinical testing p.Gly426Trp (GGG>TGG): c.1276 G>T in exon 2 of the SLC2A10 gene (NM_030777.3). Mutations in the SLC2A10 gene are associated with autosomal recessive arterial tortuosity syndrome (ATS), which is a connective tissue disorder characterized by severe tortuosity, stenosis, and aneurysms of the aorta and middle-sized arteries (Wessels M et al., 2004; Coucke P et al., 2006).The G426W mutation in the SLC2A10 gene has been previously reported in association with ATS (Callewaert B et al., 2008). Callewaert et al. (2008) identified the mutation (in conjunction with other SLCA10 mutations) in three unrelated families and it was absent from 200 control chromosomes. In addition, G426W was not observed 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 G426W mutation is located in the TMD10 functional domain of the SLC2A10 gene (Callewaert et al., 2008). In silico analysis predicts G426W is probably damaging to the protein structure/function. Finally, the G426 residue is conserved across species. In summary, G436W in the SLC2A10 gene is interpreted as a disease-causing mutation. This variant was found in TAAD
CeGaT Praxis fuer Humangenetik Tuebingen RCV000199687 SCV001250301 pathogenic not provided 2019-02-01 criteria provided, single submitter clinical testing
Invitae RCV000004851 SCV001386351 likely pathogenic Arterial tortuosity syndrome 2020-03-14 criteria provided, single submitter clinical testing This sequence change replaces glycine with tryptophan at codon 426 of the SLC2A10 protein (p.Gly426Trp). The glycine residue is highly conserved and there is a large physicochemical difference between glycine and tryptophan. This variant is present in population databases (rs121908172, ExAC 0.005%). This variant has been observed to segregate with arterial tortuosity syndrome in families (PMID: 17935213) and has been observed to be homozygous in an individual affected with thoracic aortic aneurysm (PMID: 29907982). ClinVar contains an entry for this variant (Variation ID: 4589). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
OMIM RCV000004851 SCV000025027 pathogenic Arterial tortuosity syndrome 2008-01-01 no assertion criteria provided literature only
GeneReviews RCV000004851 SCV000195653 pathogenic Arterial tortuosity syndrome 2014-09-10 no assertion criteria provided literature only

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