Submissions for variant NM_001384474.1(LOXHD1):c.3351-1G>A

dbSNP: rs868646051

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV003660877	SCV004376094	pathogenic	not provided	2023-06-29	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 982257). Disruption of this splice site has been observed in individual(s) with deafness (PMID: 33892339). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 21 of the LOXHD1 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 LOXHD1 are known to be pathogenic (PMID: 19732867, 21465660, 25792669).
Center for Molecular Medicine, Children’s Hospital of Fudan University	RCV001261865	SCV001439204	pathogenic	Autosomal recessive nonsyndromic hearing loss 77	2020-09-30	no assertion criteria provided	clinical testing