ClinVar Miner

Submissions for variant NM_194248.3(OTOF):c.1640C>T (p.Thr547Met)

gnomAD frequency: 0.00036  dbSNP: rs200191563
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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 RCV000305506 SCV000429633 uncertain significance Autosomal recessive nonsyndromic hearing loss 9 2018-01-13 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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000606571 SCV000711180 likely benign not specified 2017-06-26 criteria provided, single submitter clinical testing p.Thr547Met in exon 15 of OTOF: This variant is not expected to have clinical si gnificance because it has been identified in 0.3% (95/34410) of Latino chromosom es by Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbS NP rs200191563).
Labcorp Genetics (formerly Invitae), Labcorp RCV000909628 SCV001054444 likely benign not provided 2025-01-30 criteria provided, single submitter clinical testing
GeneDx RCV000909628 SCV002015514 uncertain significance not provided 2024-09-12 criteria provided, single submitter clinical testing Observed in the heterozygous state in a patient with prelingual sensorineural hearing loss and no second OTOF variant was detected (Morales-Angulo C et al. (2024) International Journal of Pediatric Otorhinolaryngology. 186 https://www.sciencedirect.com/science/article/pii/S0165587624002362#appsec1); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: Morales-Angulo2024[CaseReport])
Ambry Genetics RCV002519962 SCV003616476 uncertain significance Inborn genetic diseases 2021-10-06 criteria provided, single submitter clinical testing The c.1640C>T (p.T547M) alteration is located in exon 15 (coding exon 15) of the OTOF gene. This alteration results from a C to T substitution at nucleotide position 1640, causing the threonine (T) at amino acid position 547 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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