ClinVar Miner

Submissions for variant NM_194248.3(OTOF):c.4559G>A (p.Arg1520Gln)

gnomAD frequency: 0.00009  dbSNP: rs80356601
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000021063 SCV000915908 uncertain significance Autosomal recessive nonsyndromic hearing loss 9 2018-10-19 criteria provided, single submitter clinical testing The OTOF c.4559G>A (p.Arg1520Gln) variant is a missense variant that has been reported in a single study and found in one individual affected with bilateral profound prelingual hearing loss in a compound heterozygous state along with a stop-gained variant (Rouillon et al. 2006). The p.Arg1520Gln variant was absent from 100 controls and is reported at a frequency of 0.000493 in the Ashkenazi Jewish population of the Genome Aggregation Database. The evidence for this variant is limited. The p.Arg1520Gln variant is therefore classified as a variant of unknown significance but suspicious for pathogenicity for autosomal recessive nonsyndromic hearing loss. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002281713 SCV002572282 uncertain significance not specified 2022-08-23 criteria provided, single submitter clinical testing Variant summary: OTOF c.4559G>A (p.Arg1520Gln) results in a conservative amino acid change located in the C2 domain (IPR000008) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 6e-05 in 251466 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in OTOF causing Nonsyndromic Hearing Loss And Deafness, Type 9 (6e-05 vs 0.0011), allowing no conclusion about variant significance. c.4559G>A has been reported in the literature in at least one compound heterozygous individual affected with Nonsyndromic Hearing Loss And Deafness (e.g. Rouillon_2006). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted a clinical-significance assessment for this variant to ClinVar after 2014 and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Fulgent Genetics, Fulgent Genetics RCV000021063 SCV002799658 uncertain significance Autosomal recessive nonsyndromic hearing loss 9 2022-03-30 criteria provided, single submitter clinical testing
Invitae RCV003556065 SCV004292079 likely benign not provided 2023-12-22 criteria provided, single submitter clinical testing
GeneReviews RCV000021063 SCV000041719 not provided Autosomal recessive nonsyndromic hearing loss 9 no assertion provided literature only

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