ClinVar Miner

Submissions for variant NM_194248.3(OTOF):c.1630C>T (p.Arg544Cys) (rs139954767)

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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 RCV000041467 SCV000065162 uncertain significance not specified 2018-08-21 criteria provided, single submitter clinical testing The p.Arg544Cys variant in OTOF has been identified in 1 individual with autosom al recessive sensorineural hearing loss who carried a second OTOF variant of unc ertain significance; it is unclear whether these variants are in trans (Sommen 2 016). The p.Arg544Cys variant has also been identified by our laboratory in 6 in dividuals with hearing loss; however, none of these individuals carried a varian t affecting the other copy of the OTOF gene or was reported to have auditory neu ropathy typically associated with OTOF related hearing loss. This variant has be en reported in ClinVar (Variation ID: 48176). It has been identified in 0.15% (1 93/125430) of European chromosomes by the Genome Aggregation Database (gnomAD, h ttp://; however, this frequency is not high enough to rule out a pathogenic role. Computational prediction tools and conservation anal ysis suggest that the p.Arg544Cys variant may impact the protein, though this in formation is not predictive enough to determine pathogenicity. In summary, the c linical significance of the p.Arg544Cys variant is uncertain. ACMG/AMP Criteria applied: PP3, BS1_Supporting.
Illumina Clinical Services Laboratory,Illumina RCV000357820 SCV000429634 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.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000726979 SCV000704632 uncertain significance not provided 2016-12-20 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000726979 SCV001144806 uncertain significance not provided 2019-05-14 criteria provided, single submitter clinical testing

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