ClinVar Miner

Submissions for variant NM_194248.3(OTOF):c.40C>T (p.Arg14Trp)

gnomAD frequency: 0.00003  dbSNP: rs774530840
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000728063 SCV000855589 uncertain significance not provided 2017-07-25 criteria provided, single submitter clinical testing
GeneDx RCV000728063 SCV002567429 uncertain significance not provided 2022-08-19 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002535055 SCV003706452 uncertain significance Inborn genetic diseases 2021-12-06 criteria provided, single submitter clinical testing The c.40C>T (p.R14W) alteration is located in exon 1 (coding exon 1) of the OTOF gene. This alteration results from a C to T substitution at nucleotide position 40, causing the arginine (R) at amino acid position 14 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000728063 SCV004275872 likely benign not provided 2024-02-29 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System RCV000728063 SCV001551600 uncertain significance not provided no assertion criteria provided clinical testing The OTOF p.R14W variant was not identified in the literature but was identified in dbSNP (ID: rs774530840) and ClinVar (classified as uncertain significance by EGL Genetic Diagnostics). The variant was identified in control databases in 25 of 282614 chromosomes at a frequency of 0.00008846 (Genome Aggregation Database March 6, 2019, v2.1.1). The p.R14 residue is conserved in mammals and computational analyses (MUT Assesor, PolyPhen-2, SIFT, MutationTaster, Revel, FATHMM, MetaLR, DANN) suggest that the variant may impact the protein; however this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (Splice AI exome) do not predict a deleterious effect on splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

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