Submissions for variant NM_030777.4(SLC2A10):c.367G>A (p.Val123Met)

gnomAD frequency: 0.00001  dbSNP: rs770619266

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002311225	SCV000320603	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2015-12-30	criteria provided, single submitter	clinical testing	The p.V123M variant (also known as c.367G>A), located in coding exon 2 of the SLC2A10 gene, results from a G to A substitution at nucleotide position 367. The valine at codon 123 is replaced by methionine, an amino acid with highly similar properties. Based on data from ExAC, the A allele was reported in 1 of 121248 (0.0008%) total alleles (Exome Aggregation Consortium (ExAC), Cambridge, MA (URL: http://exac.broadinstitute.org) [Accessed December 28, 2015]). This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. This amino acid position is not well conserved in available vertebrate species, and methionine is the reference amino acid in two species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001217868	SCV001389726	uncertain significance	Arterial tortuosity syndrome	2024-05-01	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 123 of the SLC2A10 protein (p.Val123Met). This variant is present in population databases (rs770619266, gnomAD 0.009%). 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: 264583). 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 with a negative predictive value of 95%. 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.
CeGaT Center for Human Genetics Tuebingen	RCV002059051	SCV002496678	uncertain significance	not provided	2022-03-01	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV002059051	SCV005195015	uncertain significance	not provided		criteria provided, single submitter	not provided