Submissions for variant NM_001146079.2(CLDN14):c.254T>A (p.Val85Asp)

dbSNP: rs74315437

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
3billion, Medical Genetics	RCV000005124	SCV002521193	pathogenic	Autosomal recessive nonsyndromic hearing loss 29	2022-05-22	criteria provided, single submitter	clinical testing	The variant was co-segregated with Deafness, autosomal recessive 29 in multiple affected family members with additional meioses meeting strong evidence levels (PMID: 11163249). In silico prediction tools and conservation analysis predicted that this variant was probably damaging to the protein structure/function (REVEL: 0.947>=0.6, 3CNET: 0.755>=0.75). A missense variant is a common mechanism associated with Deafness, autosomal recessive 29. It has been reported with an extremely low frequency in the gnomAD v2.1.1 (https://gnomad.broadinstitute.org/) dataset. Amino acid change identical to known pathogenic variant has been previously reported with supporting evidence (ClinVar ID: VCV000004851, PMID:11163249). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
OMIM	RCV000005124	SCV000025301	pathogenic	Autosomal recessive nonsyndromic hearing loss 29	2012-02-01	no assertion criteria provided	literature only
Laboratory of Molecular Genetics, National Institutes of Health	RCV000417186	SCV000494728	pathogenic	Hearing impairment	2016-08-30	no assertion criteria provided	research
University of Washington Center for Mendelian Genomics, University of Washington	RCV001291511	SCV001480017	likely pathogenic	Hearing loss, autosomal recessive		no assertion criteria provided	research