Submissions for variant NM_030777.4(SLC2A10):c.366C>T (p.Tyr122=)

gnomAD frequency: 0.00411  dbSNP: rs34990188

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000128121	SCV000171713	benign	not specified	2013-02-21	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae	RCV001086887	SCV000261541	benign	Arterial tortuosity syndrome	2024-01-31	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000128121	SCV000314736	benign	not specified	2016-04-12	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000770703	SCV000317677	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2015-09-22	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Eurofins Ntd Llc (ga)	RCV000128121	SCV000333257	likely benign	not specified	2015-08-05	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001086887	SCV000605164	benign	Arterial tortuosity syndrome	2023-09-15	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000770703	SCV000902180	benign	Familial thoracic aortic aneurysm and aortic dissection	2016-06-24	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000755386	SCV001153488	likely benign	not provided	2023-09-01	criteria provided, single submitter	clinical testing	SLC2A10: BP4, BP7, BS2
Illumina Laboratory Services, Illumina	RCV001086887	SCV001301673	likely benign	Arterial tortuosity syndrome	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000128121	SCV001361148	benign	not specified	2019-12-09	criteria provided, single submitter	clinical testing	Variant summary: SLC2A10 c.366C>T results in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0047 in 251232 control chromosomes, predominantly at a frequency of 0.0067 within the South Asian subpopulation in the gnomAD database, including 2 homozygotes. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 4-folds over the estimated maximal expected allele frequency for a pathogenic variant in SLC2A10 causing Aortopathy phenotype (0.0016), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. To our knowledge, no occurrence of c.366C>T in individuals affected with Aortopathy and no experimental evidence demonstrating its impact on protein function have been reported. Six ClinVar submissions (evaluation after 2014) cite the variant four times as benign and twice as likely benign. Based on the evidence outlined above, the variant was classified as benign.
Fulgent Genetics, Fulgent Genetics	RCV001086887	SCV002795483	likely benign	Arterial tortuosity syndrome	2021-09-13	criteria provided, single submitter	clinical testing