ClinVar Miner

Submissions for variant NM_001039141.3(TRIOBP):c.5705A>C (p.Lys1902Thr)

gnomAD frequency: 0.00071  dbSNP: rs138804394
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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 RCV000219620 SCV000272558 uncertain significance not specified 2020-11-10 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Lys1902Thr variant in TRIOBP has been reported by our laboratory in six individuals with sensorineural hearing loss. None of these individuals carried a second pathogenic variant in TRIOBP gene, and two individuals had an alternate etiology identified. It has been identified in 0.1% (31/26602) of South Asian chromosomes and 0.09% (99/105770) of European chromosomes including 1 homozygote by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs138804394). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. This variant has also been reported in ClinVar (Variation ID 229363). Computational prediction tools and conservation analysis suggest that the p.Lys1902Thr variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, while the clinical significance of the p.Lys1902Thr variant is uncertain, its frequency suggests it is more likely to be benign. ACMG/AMP Criteria applied: PP3, BS1_Supporting.
Eurofins Ntd Llc (ga) RCV000727151 SCV000706169 uncertain significance not provided 2018-04-25 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000765639 SCV000896968 uncertain significance Autosomal recessive nonsyndromic hearing loss 28 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000727151 SCV001764301 uncertain significance not provided 2021-07-02 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27535533)
CeGaT Center for Human Genetics Tuebingen RCV000727151 SCV002585930 uncertain significance not provided 2022-08-01 criteria provided, single submitter clinical testing
Invitae RCV000727151 SCV003257423 uncertain significance not provided 2022-08-09 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 1902 of the TRIOBP protein (p.Lys1902Thr). This variant is present in population databases (rs138804394, gnomAD 0.1%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with TRIOBP-related conditions. ClinVar contains an entry for this variant (Variation ID: 229363). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Mayo Clinic Laboratories, Mayo Clinic RCV000727151 SCV004225608 uncertain significance not provided 2022-04-13 criteria provided, single submitter clinical testing BS1_supporting
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000727151 SCV001959285 uncertain significance not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000727151 SCV001975845 uncertain significance not provided no assertion criteria provided clinical testing

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