ClinVar Miner

Submissions for variant NM_173477.5(USH1G):c.837C>G (p.Asp279Glu) (rs142486910)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000155318 SCV000205004 uncertain significance not specified 2015-09-08 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Asp279Glu var iant in USH1G has now been identified by our laboratory in 3 individuals with he aring loss; however, an alternate explanation of the hearing loss was identified in 1 family. This variant has also been identified in 0.1% (55/64670) of Europe an chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinsti tute.org; dbSNP rs142486910). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. Co mputational prediction tools and conservation analysis suggest that the p.Asp279 Glu variant may not impact the protein, though this information is not predictiv e enough to rule out pathogenicity. In summary, while the clinical significance of the p.Asp279Glu variant is uncertain, these data suggest that it is more like ly to be benign.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000725682 SCV000338572 uncertain significance not provided 2016-01-25 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000999863 SCV000884835 uncertain significance Usher syndrome, type 1G 2018-11-07 criteria provided, single submitter clinical testing The p.Asp279Glu variant (rs142486910) has not been reported in the medical literature nor has it been previously identified in our laboratory; however, it is listed in the ClinVar database as a variant of uncertain significance (Variation ID: 178570). It is listed in the Genome Aggregation Database (gnomAD) browser with a frequency in Ashkenazi Jewish individuals of 0.56% (identified in 57 out of 10,112 chromosomes). The aspartic acid at codon 279 is not highly conserved (Alamut software v2.9), and several species including zebra finch and Xenopus tropical have a glutamic acid at this position suggesting this change is evolutionary tolerated. Furthermore, computational analyses suggest this variant does not have a significant effect on USH1G protein structure/function (SIFT: tolerated, PolyPhen2: benign, and Mutation Taster: polymorphism). However, based on the available information, the clinical significance of the p.Asp279Glu variant cannot be determined with certainty.
Invitae RCV000725682 SCV001054580 likely benign not provided 2019-12-31 criteria provided, single submitter clinical testing

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