ClinVar Miner

Submissions for variant NM_030777.4(SLC2A10):c.394C>T (p.Arg132Trp) (rs121908173)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000619910 SCV000739644 uncertain significance Cardiovascular phenotype 2016-04-21 criteria provided, single submitter clinical testing The p.R132W variant (also known as c.394C>T), located in coding exon 2 of the SLC2A10 gene, results from a C to T substitution at nucleotide position 394. The arginine at codon 132 is replaced by tryptophan, an amino acid with dissimilar properties. This variant was reported in three families with arterial tortuosity syndrome and in one family a frameshift mutation was present in the second allele (Callewaert BL et al, Hum. Mutat. 2008 Jan; 29(1):150-8). This variant was previously reported in the SNPDatabase as rs121908173. Based on data from ExAC, the T allele has an overall frequency of approximately <0.01% (1/106171). This variant was not reported in population based cohorts in the following databases: NHLBI Exome Sequencing Project (ESP) and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.
Fulgent Genetics,Fulgent Genetics RCV000004852 SCV000895251 uncertain significance Arterial tortuosity syndrome 2018-10-31 criteria provided, single submitter clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000004852 SCV001468392 likely pathogenic Arterial tortuosity syndrome 2020-06-11 criteria provided, single submitter clinical testing SLC2A10 NM_030777.3 exon 2 p.Arg132Trp (c.394C>T): This variant has been reported in the literature in the compound heterozygous state with another pathogenic variant, in at least 5 individuals with aterial tortuosity syndrome, segregating with disease in one affected family member (Callewaert 2008 PMID:17935213, Hardin 2018 PMID:28726533, Weerakkody 2018 PMID:29543232). This variant is present in 0.005% (7/129070) of European alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/20-45354069-C-T). Please note, disease causing variants may be present in control databases at low frequencies, reflective of the general population, carrier status, and/or variable expressivity. This variant is present in ClinVar (Variation ID:4590). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is highly suspicious for disease, but requires further evidence for pathogenicity. Therefore, this variant is classified as likely pathogenic.
GeneDx RCV001558568 SCV001780546 likely pathogenic not provided 2021-05-20 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Reported in ClinVar (ClinVar Variant ID# 4590; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 29543232, 17935213, 28726533, 25392904)
OMIM RCV000004852 SCV000025028 pathogenic Arterial tortuosity syndrome 2008-01-01 no assertion criteria provided literature only
GeneReviews RCV000004852 SCV000195646 pathogenic Arterial tortuosity syndrome 2014-09-10 no assertion criteria provided literature only
Centre for Genomic and Experimental Medicine,University of Edinburgh RCV000616750 SCV000731235 likely pathogenic Familial thoracic aortic aneurysm and aortic dissection no assertion criteria provided research

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