ClinVar Miner

Submissions for variant NM_030777.4(SLC2A10):c.1330C>T (p.Arg444Ter) (rs370547023)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000492992 SCV000583136 likely pathogenic not provided 2017-05-12 criteria provided, single submitter clinical testing The R444X variant in the SLC2A10 gene has been reported in an Italian patient who was compound heterozygous for theR444X nonsense variant and the E437K missense variant (Drera et al., 2007). Drera et al. (2007) describe a 14 year old child with clinical features of ATS including stenosis, and tortuosity of the left pulmonary artery, tortuosity of carotid, vertebral, and intracerebral arteries and a family history significant for two deceased siblings with findings suggestive of ATS. R444X is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Nemeth et al. (2016) performed in vivo studies from fibroblasts of the patient described by Drera et al. (2007) demonstrating the absence of mRNA due to nuclear mediated decay, with restoration of normal endomembrane transport of DAA when transfected with wild-type SCL10A2. Other nonsense variants in the SLC2A10 gene have been reported in Human Gene Mutation Database in association with ATS (Stenson et al., 2014). Furthermore, the R444X variant is not observed at asignificant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome VariantServer). In summary, although R444X in the SLC2A10 gene is interpreted as a likely pathogenic variant
Invitae RCV000202558 SCV001234205 pathogenic Arterial tortuosity syndrome 2019-01-26 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg444*) in the SLC2A10 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with arterial tortuosity syndrome (PMID: 17163528). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 161101). Loss-of-function variants in SLC2A10 are known to be pathogenic (PMID: 17935213, 22488877, 23494979). For these reasons, this variant has been classified as Pathogenic.
GeneReviews RCV000202558 SCV000195655 pathogenic Arterial tortuosity syndrome 2014-09-10 no assertion criteria provided literature only

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