Submissions for variant NM_030777.4(SLC2A10):c.504C>A (p.Phe168Leu)

dbSNP: rs540023880

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000199476	SCV000250737	uncertain significance	not provided	2018-11-26	criteria provided, single submitter	clinical testing	The F168L variant of uncertain significance in the SLC2A10 gene has not been published in association with ATS to our knowledge. This variant is observed in 26/246090 (0.01%) alleles from individuals of multiple ethnic backgrounds, including one homozygous individual, in large population cohorts indicating this may be a rare benign variant (Lek et al., 2016). The F168L variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Nevertheless, in-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001192939	SCV001361408	uncertain significance	not specified	2019-10-08	criteria provided, single submitter	clinical testing	Variant summary: SLC2A10 c.504C>A (p.Phe168Leu) results in a non-conservative amino acid change located in the Major facilitator superfamily domain (IPR020846) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0001 in 251300 control chromosomes in the gnomAD database, including 1 homozygotes. This frequency is not significantly higher than expected for a pathogenic variant in SLC2A10 causing Aortopathy (0.0001 vs 0.0016), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.504C>A in individuals affected with Aortopathy and no experimental evidence demonstrating its impact on protein function have been reported. A ClinVar submission (evaluation after 2014) cites the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002054312	SCV002493867	likely benign	Arterial tortuosity syndrome	2022-11-12	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002336533	SCV002641858	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2024-09-30	criteria provided, single submitter	clinical testing	The p.F168L variant (also known as c.504C>A), located in coding exon 2 of the SLC2A10 gene, results from a C to A substitution at nucleotide position 504. The phenylalanine at codon 168 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species; however, leucine is the reference amino acid in other 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.