Submissions for variant NM_030777.4(SLC2A10):c.173C>T (p.Ala58Val)

gnomAD frequency: 0.00001  dbSNP: rs141310869

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001138753	SCV001298829	uncertain significance	Arterial tortuosity syndrome	2018-01-13	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001138753	SCV004514683	uncertain significance	Arterial tortuosity syndrome	2023-10-04	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 58 of the SLC2A10 protein (p.Ala58Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with arterial tortuosity syndrome (Invitae). ClinVar contains an entry for this variant (Variation ID: 896230). 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. 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.
Ambry Genetics	RCV004671227	SCV005164626	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2024-04-17	criteria provided, single submitter	clinical testing	The p.A58V variant (also known as c.173C>T), located in coding exon 2 of the SLC2A10 gene, results from a C to T substitution at nucleotide position 173. The alanine at codon 58 is replaced by valine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.