ClinVar Miner

Submissions for variant NM_001146079.2(CLDN14):c.242G>A (p.Arg81His)

gnomAD frequency: 0.00001  dbSNP: rs368027306
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Department of Otolaryngology – Head & Neck Surgery, Cochlear Implant Center RCV001375151 SCV001572109 likely pathogenic Hearing impairment 2021-04-12 criteria provided, single submitter clinical testing PS1_Strong, PM2_Moderate, PP3_Supporting
GeneDx RCV002272154 SCV002558665 likely pathogenic not provided 2022-01-28 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 23235333, 31527509, 29447821, 22246673)
Labcorp Genetics (formerly Invitae), Labcorp RCV002272154 SCV003443976 pathogenic not provided 2022-01-05 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 81 of the CLDN14 protein (p.Arg81His). This variant is present in population databases (rs368027306, gnomAD 0.01%). This missense change has been observed in individuals with deafness (PMID: 22246673, 23235333). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 189331). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics, part of Exact Sciences RCV003422062 SCV004118507 likely pathogenic CLDN14-related disorder 2022-08-18 criteria provided, single submitter clinical testing The CLDN14 c.242G>A variant is predicted to result in the amino acid substitution p.Arg81His. This variant was reported to segregate with autosomal recessive nonsyndromic hearing loss in six affected and one unaffected member of a consanguineous family and a single affected member of a second family (Lee et al 2012. PubMed ID: 22246673; Bashir et al 2012. PubMed ID: 23235333). This variant is reported in 0.0062% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/21-37833752-C-T). This variant is interpreted as likely pathogenic.
OMIM RCV000169747 SCV000221297 pathogenic Autosomal recessive nonsyndromic hearing loss 29 2012-02-01 no assertion criteria provided literature only

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