Submissions for variant NM_030777.4(SLC2A10):c.1600C>T (p.Arg534Cys)

gnomAD frequency: 0.00013  dbSNP: rs142577271

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000198411	SCV000250731	uncertain significance	not provided	2023-08-22	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
Labcorp Genetics (formerly Invitae), Labcorp	RCV000526612	SCV000644161	uncertain significance	Arterial tortuosity syndrome	2025-01-23	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 534 of the SLC2A10 protein (p.Arg534Cys). This variant is present in population databases (rs142577271, gnomAD 0.02%). 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: 213742). Invitae Evidence 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 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	RCV001171033	SCV000739647	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2025-02-17	criteria provided, single submitter	clinical testing	The p.R534C variant (also known as c.1600C>T), located in coding exon 5 of the SLC2A10 gene, results from a C to T substitution at nucleotide position 1600. The arginine at codon 534 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001171033	SCV001333702	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2019-01-25	criteria provided, single submitter	clinical testing