ClinVar Miner

Submissions for variant NM_030777.4(SLC2A10):c.781G>A (p.Val261Ile)

gnomAD frequency: 0.00019  dbSNP: rs372561968
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000253424 SCV000319358 uncertain significance Cardiovascular phenotype 2014-11-21 criteria provided, single submitter clinical testing There is insufficient or conflicting evidence for classification of this alteration.
Invitae RCV000459737 SCV000549178 uncertain significance Arterial tortuosity syndrome 2022-10-25 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 261 of the SLC2A10 protein (p.Val261Ile). This variant is present in population databases (rs372561968, gnomAD 0.03%). 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: 263879). 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.
Illumina Laboratory Services, Illumina RCV000459737 SCV001296468 uncertain significance Arterial tortuosity syndrome 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx RCV001536754 SCV001753560 uncertain significance not provided 2021-06-24 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 26582918, 27535533)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003317174 SCV004021238 uncertain significance not specified 2023-06-19 criteria provided, single submitter clinical testing Variant summary: SLC2A10 c.781G>A (p.Val261Ile) results in a conservative amino acid change located in the Major facilitator superfamily domain (IPR020846) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8.8e-05 in 251104 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in SLC2A10 causing Arterial Tortuosity Syndrome (8.8e-05 vs 0.0016), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.781G>A in individuals affected with Arterial Tortuosity Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Three ClinVar submitters have assessed this variant since 2014: all submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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