Submissions for variant NM_194248.3(OTOF):c.4227+1G>T

gnomAD frequency: 0.00009  dbSNP: rs397515601

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV003556145	SCV004292082	pathogenic	not provided	2024-01-19	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 34 of the OTOF gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in OTOF are known to be pathogenic (PMID: 18381613, 19250381, 22575033). This variant is present in population databases (rs397515601, gnomAD 0.003%). Disruption of this splice site has been observed in individual(s) with deafness (PMID: 18381613). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 65802). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
GeneReviews	RCV000056041	SCV000087101	not provided	Autosomal recessive nonsyndromic hearing loss 9		no assertion provided	literature only
Genetic Testing Center for Deafness, Department of Otolaryngology Head & Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital	RCV000056041	SCV000902352	likely pathogenic	Autosomal recessive nonsyndromic hearing loss 9	2019-02-26	no assertion criteria provided	case-control