Submissions for variant NM_030777.4(SLC2A10):c.929C>T (p.Ser310Phe)

gnomAD frequency: 0.00002  dbSNP: rs763521707

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000199139	SCV000250720	uncertain significance	not provided	2019-09-06	criteria provided, single submitter	clinical testing	Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp	RCV001857724	SCV002252810	uncertain significance	Arterial tortuosity syndrome	2024-01-18	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 310 of the SLC2A10 protein (p.Ser310Phe). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 213732). 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	RCV002372176	SCV002686548	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2023-01-23	criteria provided, single submitter	clinical testing	The c.929C>T (p.S310F) alteration is located in exon 2 (coding exon 2) of the SLC2A10 gene. This alteration results from a C to T substitution at nucleotide position 929, causing the serine (S) at amino acid position 310 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV002372176	SCV003838258	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2022-02-15	criteria provided, single submitter	clinical testing
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital	RCV000582570	SCV000692259	uncertain significance	Bicuspid aortic valve	2015-11-19	no assertion criteria provided	clinical testing