ClinVar Miner

Submissions for variant NM_030777.4(SLC2A10):c.1423T>G (p.Leu475Val)

gnomAD frequency: 0.00001  dbSNP: rs754355572
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000200749 SCV000250729 uncertain significance not provided 2013-01-08 criteria provided, single submitter clinical testing p.Leu475Val (TTG>GTG): c.1423 T>G in exon 4 of the SLC2A10 gene (NM_030777.3). The Leu475Val variant in the SLC2A10 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Leu475Val results in a conservative amino acid substitution of one non-polar amino acid with another at a position that is conserved in mammals. In silico analysis predicts possibly damaging to the protein structure/function. The NHLBI ESP Exome Variant Server reports Leu475Val was not observed in approximately 6,500 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. Nevertheless, no mutations in nearby codons have been reported in association with arterial tortuosity syndrome. With the clinical and molecular information available at this time, we cannot definitively determine if Leu475Val is a disease-causing mutation or a rare benign variant. This variant was found in TAAD
Labcorp Genetics (formerly Invitae), Labcorp RCV000702084 SCV000830918 uncertain significance Arterial tortuosity syndrome 2022-08-23 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 475 of the SLC2A10 protein (p.Leu475Val). This variant is present in population databases (rs754355572, gnomAD 0.01%). 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: 213740). 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.
Ambry Genetics RCV002390519 SCV002698649 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-08-04 criteria provided, single submitter clinical testing The c.1423T>G (p.L475V) alteration is located in exon 4 (coding exon 4) of the SLC2A10 gene. This alteration results from a T to G substitution at nucleotide position 1423, causing the leucine (L) at amino acid position 475 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.