Submissions for variant NM_030777.4(SLC2A10):c.1370C>T (p.Ala457Val)

gnomAD frequency: 0.00015  dbSNP: rs201393026

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000766833	SCV000250726	uncertain significance	not provided	2017-09-08	criteria provided, single submitter	clinical testing	The A457V variant of uncertain significance in the SLC2A10 gene has not been published as pathogenic or benign to our knowledge. This variant has been identified, in conjunction with additional cardiogenetic variants, in other unrelated individuals referred for Marfan syndrome/TAAD genetic testing at GeneDx. However, thus far, segregation data is limited or absent for these individuals due to the lack of clinical information provided and insufficient participation by informative family members. The A457V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In addition, this substitution also occurs at a position where amino acids with similar properties to alanine are tolerated across species, and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function Furthermore, A457V is observed in 22/66,740 alleles from individuals of European (Non-Finnish) ancestry in the Exome Aggregation Consortium (ExAC) database (Lek et al., 2016).
Ambry Genetics	RCV002311060	SCV000320580	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2023-02-08	criteria provided, single submitter	clinical testing	The p.A457V variant (also known as c.1370C>T), located in coding exon 3 of the SLC2A10 gene, results from a C to T substitution at nucleotide position 1370. The alanine at codon 457 is replaced by valine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species; however, valine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Illumina Laboratory Services, Illumina	RCV000356436	SCV000434168	uncertain significance	Arterial tortuosity syndrome	2018-01-12	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000356436	SCV000605162	uncertain significance	Arterial tortuosity syndrome	2019-09-25	criteria provided, single submitter	clinical testing	The SLC2A10 c.1370C>T; p.Ala457Val variant (rs201393026), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 213737). This variant is found in the general population with an allele frequency of 0.024% (67/282,878 alleles) in the Genome Aggregation Database. The alanine at codon 457 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Due to limited information, the clinical significance of this variant is uncertain at this time.
Invitae	RCV000356436	SCV000644158	likely benign	Arterial tortuosity syndrome	2024-01-15	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000766833	SCV001502394	uncertain significance	not provided	2020-09-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003114355	SCV003801207	uncertain significance	not specified	2023-01-01	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV002311060	SCV003838918	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2021-06-01	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000766833	SCV004225501	uncertain significance	not provided	2023-02-22	criteria provided, single submitter	clinical testing
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital	RCV000581259	SCV000692261	uncertain significance	Aortic aneurysm, familial thoracic 2	2016-11-08	no assertion criteria provided	clinical testing