Submissions for variant NM_030777.4(SLC2A10):c.1154C>G (p.Ala385Gly)

gnomAD frequency: 0.01835  dbSNP: rs79849424

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000128124	SCV000171716	benign	not specified	2013-04-15	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	RCV000230382	SCV000290944	benign	Arterial tortuosity syndrome	2024-01-26	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000128124	SCV000314727	benign	not specified		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002310712	SCV000317384	benign	Familial thoracic aortic aneurysm and aortic dissection	2015-04-02	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Illumina Laboratory Services, Illumina	RCV000230382	SCV000434164	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000230382	SCV000743111	benign	Arterial tortuosity syndrome	2016-03-30	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000128124	SCV001361149	benign	not specified	2019-08-19	criteria provided, single submitter	clinical testing	Variant summary: SLC2A10 c.1154C>G (p.Ala385Gly) results in a non-conservative amino acid change located in the Major facilitator superfamily domain (IPR020846) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.011 in 251270 control chromosomes in the gnomAD database, including 81 homozygotes. The observed variant frequency is approximately 7.0 fold of the estimated maximal expected allele frequency for a pathogenic variant in SLC2A10 causing Aortopathy phenotype (0.0016), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.1154C>G in individuals affected with Aortopathy and no experimental evidence demonstrating its impact on protein function have been reported. Co-occurrences with other pathogenic variant(s) have been reported at our laboratory (FBN1 c.349C>T, p.Q117*), providing supporting evidence for a benign role. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000230382	SCV002048650	benign	Arterial tortuosity syndrome	2023-10-19	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV002310712	SCV004239695	benign	Familial thoracic aortic aneurysm and aortic dissection	2022-11-17	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000230382	SCV000745580	benign	Arterial tortuosity syndrome	2014-02-04	no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001573811	SCV001800204	likely benign	not provided		no assertion criteria provided	clinical testing