Submissions for variant NM_030777.4(SLC2A10):c.313C>T (p.Arg105Cys)

gnomAD frequency: 0.00005  dbSNP: rs767864243

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000202814	SCV000258207	uncertain significance	not specified	2015-06-25	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002310718	SCV000319646	pathogenic	Familial thoracic aortic aneurysm and aortic dissection	2015-05-08	criteria provided, single submitter	clinical testing	The p.R105C pathogenic mutation (also known as c.313C>T), located in coding exon 2 of the SLC2A10 gene, results from a C to T substitution at nucleotide position 313. The arginine at codon 105 is replaced by cysteine, an amino acid with highly dissimilar properties. This variant has been described in a consanguineous Saudi Arabian family in which one individual was affected with arterial tortuosity syndrome (ATS). The affected individual was homozygous for the variant and both of his unaffected parents were confirmed to be heterozygous (Faiyaz-Ul-Haque M et al. Atherosclerosis 2009;203(2):466-71). This alteration has also been reported in a second individual with ATS in the compound heterozygous state with the recurrent SLC2A10 nonsense mutation p.G445Efs*40 (Hardin JS et al. Ophthalmic Genet. 2018;39:29-34). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
Invitae	RCV000202447	SCV000644163	pathogenic	Arterial tortuosity syndrome	2023-10-13	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 105 of the SLC2A10 protein (p.Arg105Cys). This variant is present in population databases (rs767864243, gnomAD 0.009%). This missense change has been observed in individuals with clinical features of arterial tortuosity syndrome (PMID: 18774132, 28726533; Invitae). ClinVar contains an entry for this variant (Variation ID: 161104). 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 expected to disrupt SLC2A10 protein function. This variant disrupts the p.Arg105 amino acid residue in SLC2A10. Other variant(s) that disrupt this residue have been observed in individuals with SLC2A10-related conditions (PMID: 28726533), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen	RCV000997782	SCV001153486	likely pathogenic	not provided	2019-05-01	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000202447	SCV001521671	likely pathogenic	Arterial tortuosity syndrome		criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004526620	SCV005039868	likely pathogenic	Familial aortopathy	2024-03-18	criteria provided, single submitter	clinical testing	Variant summary: SLC2A10 c.313C>T (p.Arg105Cys) results in a non-conservative amino acid change located in the Major facilitator superfamily domain (IPR020846) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 250838 control chromosomes. c.313C>T has been reported in the literature in individuals affected with Aortopathy. These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. ClinVar contains an entry for this variant (Variation ID: 161104). Based on the evidence outlined above, the variant was classified as likely pathogenic.
GeneReviews	RCV000202447	SCV000195658	not provided	Arterial tortuosity syndrome		no assertion provided	literature only