ClinVar Miner

Submissions for variant NM_194248.3(OTOF):c.245G>A (p.Arg82His) (rs149766574)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000041499 SCV000065194 benign not specified 2012-05-16 criteria provided, single submitter clinical testing Arg82His in Exon 04 of OTOF: This variant is not expected to have clinical signi ficance because it has been identified in 0.6% (24/3738) of African American chr omosomes from a broad population by the NHLBI Exome Sequencing Project (http://e; dbSNP rs149766574).
Illumina Clinical Services Laboratory,Illumina RCV000785039 SCV000429656 uncertain significance Deafness, autosomal recessive 9 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.
GeneDx RCV000767023 SCV000620270 uncertain significance not provided 2017-08-24 criteria provided, single submitter clinical testing The R82H variant in the OTOF gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. It is reported as benign in ClinVar by a different clinical laboratory, but additional evidence is not available (ClinVar SCV000065194.4; Landrum et al., 2015). The R82H variant is observed in 50/7412 (0.68%) alleles from individuals of African background in the ExAC dataset, and no individuals were reported to be homozygous (Lek et al., 2016). The R82H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret R82H as a variant of uncertain significance.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000041499 SCV000860989 likely benign not specified 2018-04-30 criteria provided, single submitter clinical testing
Genomic Research Center,Shahid Beheshti University of Medical Sciences RCV000785039 SCV000923592 uncertain significance Deafness, autosomal recessive 9 2019-01-01 criteria provided, single submitter clinical testing
Invitae RCV000767023 SCV001039162 likely benign not provided 2019-12-31 criteria provided, single submitter clinical testing
National Institute on Deafness and Communication Disorders,National Institutes of Health RCV001543606 SCV001519356 uncertain significance Childhood onset hearing loss 2021-07-08 criteria provided, single submitter research PP3 (non REVEL) / Modifications from PMID: 30311386 for classification: The genetic causes of hearing loss have not yet been well characterized in the Yoruba population, and the information regarding variant MAF in this population is still limited, so we did not exclude any variant based on their "high" MAF. PP3 criteria was applied even if the REVEL score was below 0.7, if at least two of the pathogenicity prediction algorithms used predicted that the variant was damaging or likely damaging.

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