Submissions for variant NM_030777.4(SLC2A10):c.1096C>T (p.Pro366Ser)

gnomAD frequency: 0.00001  dbSNP: rs774664650

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000195875	SCV000250721	uncertain significance	not provided	2018-04-25	criteria provided, single submitter	clinical testing	p.Pro366Ser (CCA>TCA): c.1096 C>T in exon 2 of the SLC2A10 gene (NM_030777.3). The Pro366Ser variant in the SLC2A10 gene has not been reported as a disease-causing mutation nor as a benign polymorphism to our knowledge. Pro366Ser results in a non-conservative amino acid substitution of a non-polar Proline with a neutral, polar Serine at a position that is not well conserved across species. In silico analysis predicts Pro366Ser is benign to the protein structure/function. No mutations in nearby residues have been reported in association with arterial tortuosity syndrome (ATS). Nevertheless, the Pro366Ser variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. With the clinical and molecular information available at this time, we cannot definitively determine if Pro366Ser is a disease-causing mutation or a rare benign variant. This variant was found in TAAD
Labcorp Genetics (formerly Invitae), Labcorp	RCV001367371	SCV001563719	uncertain significance	Arterial tortuosity syndrome	2021-08-28	criteria provided, single submitter	clinical testing	This sequence change replaces proline with serine at codon 366 of the SLC2A10 protein (p.Pro366Ser). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and serine. This variant is present in population databases (rs774664650, ExAC 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: 213733). 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.