Submissions for variant NM_015404.4(WHRN):c.1075G>A (p.Val359Ile)

gnomAD frequency: 0.00053  dbSNP: rs147500559

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000330120	SCV000343174	likely benign	not specified	2016-07-15	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000366983	SCV000476790	uncertain significance	Usher syndrome type 2D	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV000271876	SCV000476791	uncertain significance	Autosomal recessive nonsyndromic hearing loss 31	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000330120	SCV000711013	likely benign	not specified	2016-06-21	criteria provided, single submitter	clinical testing	p.Val359Ile in exon 4 of DFNB31: This variant is not expected to have clinical s ignificance due to a lack of conservation across species, including mammals. Of note, three mammals (cow, hedgehog, and platypus) have an isoleucine (Ile) at th is position despite high nearby amino acid conservation. In addition, computatio nal prediction tools do not suggest a high likelihood of impact to the protein. This variant has been identified in 0.2% (21/10300) of African chromosomes by th e Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs14 7500559).
Invitae	RCV000880644	SCV001023758	likely benign	not provided	2023-10-03	criteria provided, single submitter	clinical testing
GeneDx	RCV000880644	SCV001818417	likely benign	not provided	2020-10-13	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003940063	SCV004751006	likely benign	WHRN-related condition	2022-07-11	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).