ClinVar Miner

Submissions for variant NM_030777.4(SLC2A10):c.808G>A (p.Val270Met)

gnomAD frequency: 0.00015  dbSNP: rs749220947
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001171028 SCV001333697 likely benign Familial thoracic aortic aneurysm and aortic dissection 2018-05-07 criteria provided, single submitter clinical testing
Invitae RCV001337721 SCV001531331 uncertain significance Arterial tortuosity syndrome 2022-07-05 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 270 of the SLC2A10 protein (p.Val270Met). This variant is present in population databases (rs749220947, gnomAD 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: 915746). 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) performed at Invitae indicates that this missense variant is not expected to disrupt SLC2A10 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.
GeneDx RCV001751300 SCV001987910 uncertain significance not provided 2019-11-04 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 25363768)
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV001337721 SCV002495963 uncertain significance Arterial tortuosity syndrome 2021-03-30 criteria provided, single submitter clinical testing SLC2A10 NM_030777.3 exon 2 p.Val270Met (c.808G>A): This variant has been reported in the literature in the heterozygous state as de novo in one individual with autism (Iossifov 2014 PMID:25363768). This variant is present in 0.03% (4/10628) of Finnish alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/20-46725844-G-A?dataset=gnomad_r3) and is present in ClinVar (Variation ID:915746). This variant amino acid Methionine (Met) is present in 5 species including the multiple primates and other mammals, and it is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Ambry Genetics RCV001171028 SCV002677094 likely benign Familial thoracic aortic aneurysm and aortic dissection 2020-02-06 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: 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.

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