ClinVar Miner

Submissions for variant NM_015404.4(WHRN):c.1943C>A (p.Ser648Tyr)

gnomAD frequency: 0.00098  dbSNP: rs142653982
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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) RCV000724278 SCV000233131 uncertain significance not provided 2014-12-19 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000180652 SCV000603297 uncertain significance not specified 2019-03-18 criteria provided, single submitter clinical testing The WHRN c.1943C>A; p.Ser648Tyr variant (rs142653982; ClinVar Variation ID: 199139) is found in the general population with an overall allele frequency of 0.04% (110/281,586 alleles) in the Genome Aggregation Database. The serine at position 648 is moderately conserved (Alamut software v2.11) and computational analyses (SIFT, PolyPhen-2) of the effects of the p.Ser648Tyr variant on protein structure and function predict a deleterious effect. WHRN variants p.Ser648Tyr and p.Arg882Ser have been identified in multiple hearing loss cohorts (Aller 2010, Audo 2012, and Sloan-Heggen 2016). However, in at least one of these cohorts (Audo 2012) both variants were identified on the same chromosome and no other variants were identified in WHRN. Furthermore, neither variant has been identified in trans with any other pathogenic variant of WHRN. Therefore, the clinical significance of the p.Ser648Tyr and p.Arg882Ser variants cannot be determined with certainty. References: Aller et al. Sequence variants of the DFNB31 gene among Usher syndrome patients of diverse origin. Mol Vis. 2010 Mar 23;16:495-500. Audo et al. Development and application of a next-generation-sequencing (NGS) approach to detect known and novel gene defects underlying retinal diseases. Orphanet J Rare Dis. 2012 Jan 25;7:8. Sloan-Heggen et al. Comprehensive genetic testing in the clinical evaluation of 1119 patients with hearing loss. Hum Genet. 2016 Apr;135(4):441-50.
Labcorp Genetics (formerly Invitae), Labcorp RCV000724278 SCV001704529 likely benign not provided 2025-01-14 criteria provided, single submitter clinical testing
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg RCV004816313 SCV005070251 uncertain significance Retinal dystrophy 2023-01-01 criteria provided, single submitter clinical testing
Laboratory of Prof. Karen Avraham, Tel Aviv University RCV004698339 SCV005199917 likely pathogenic Autosomal recessive nonsyndromic hearing loss 31 2024-08-20 criteria provided, single submitter research The p.(Ser648Tyr) known recessive variant (PMID: 20352026) was detected in an hearing impaired individual with severe-to-profound HL, in compound heterozygosity with another known variant, p.(Arg882Ser).

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