ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.11366T>C (p.Ile3789Thr)

gnomAD frequency: 0.00006  dbSNP: rs183979371
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000221034 SCV000272885 uncertain significance not specified 2015-12-21 criteria provided, single submitter clinical testing The p.Ile3789Thr variant in USH2A has not been previously reported in individual s with hearing loss or Usher syndrome but has been identified in 4/11576 of Lati no chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinsti tute.org; dbSNP rs183979371); however this frequency is not high enough to rule out a pathogenic role. Computational prediction tools and conservation analysis suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical signific ance of the p.Ile3789Thr variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp RCV001047373 SCV001211325 uncertain significance not provided 2022-09-27 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 3789 of the USH2A protein (p.Ile3789Thr). This variant is present in population databases (rs183979371, gnomAD 0.05%). This missense change has been observed in individual(s) with retinitis pigmentosa (Invitae). ClinVar contains an entry for this variant (Variation ID: 229615). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Blueprint Genetics RCV001075000 SCV001240610 uncertain significance Retinal dystrophy 2017-12-22 criteria provided, single submitter clinical testing
GeneDx RCV001047373 SCV001875269 uncertain significance not provided 2024-07-26 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
3billion, Medical Genetics RCV001274942 SCV003841760 uncertain significance Usher syndrome type 2A 2023-02-23 criteria provided, single submitter clinical testing The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.007%). Therefore, this variant is classified as VUS according to the recommendation of ACMG/AMP guideline.
Genome-Nilou Lab RCV003454601 SCV004182111 uncertain significance Retinitis pigmentosa 39 2023-11-04 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001274942 SCV004182112 uncertain significance Usher syndrome type 2A 2023-11-04 criteria provided, single submitter clinical testing
Breakthrough Genomics, Breakthrough Genomics RCV001047373 SCV005187234 uncertain significance not provided criteria provided, single submitter not provided
Natera, Inc. RCV001274942 SCV001459525 uncertain significance Usher syndrome type 2A 2019-11-11 no assertion criteria provided clinical testing

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