ClinVar Miner

Submissions for variant NM_032119.4(ADGRV1):c.6559A>G (p.Ile2187Val) (rs200512504)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000155945 SCV000205657 likely benign not specified 2013-08-16 criteria provided, single submitter clinical testing Ile2187Val in exon 30 of GPR98: This variant is not expected to have clinical si gnificance due to a lack of conservation across species, including mammals. Of n ote, guinea pig, rabbit, tenrec, stickleback, medaka, and lamprey have a valine (Val) at this position despite high nearby amino acid conservation. In addition, computational analyses (PolyPhen2, SIFT, AlignGVGD) do not suggest a high likel ihood of impact to the protein. Furthermore, this variant has been identified in 1% (2/200) of Han Chinese chromosomes by the 1000 Genomes Project (dbSNP rs2005 12504). This variant has been reported in the literature homozygous in one indiv idual with hearing loss (Yang 2013); however, this individual is reported to be of Han Chinese ancestry, which is consistent with a higher frequency of this var iant in that population.
Soonchunhyang University Bucheon Hospital,Soonchunhyang University Medical Center RCV000490254 SCV000267349 uncertain significance Usher syndrome, type 2C 2016-03-18 criteria provided, single submitter reference population
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000755792 SCV000883365 likely benign not provided 2018-01-18 criteria provided, single submitter clinical testing The p.Ile2187Val variant (rs200512504) has been previously reported as a homozygote in a Chinese patient included in a cohort of non-syndromic hearing loss patients (Yang 2013). The variant was also identified in deaf relatives, and no other significant variants were identified in 78 other deafness-associated genes. However, this variant is listed in the Genome Aggregation Database (gnomAD) browser with a frequency in East Asians of 1.4% (identified in 270 out of 18,802 chromosomes). Additionally, isoleucine and valine have similar physiochemical properties (Alamut software v2.9), and species of hare, rodent, and fish have a valine at codon 2187 suggesting this change is evolutionary tolerated. This variant is also not predicted to influence ADGRV1 mRNA splicing (Alamut software v2.9), and is listed in the ClinVar database as likely benign (Variation ID: 179159). Therefore, the p.Ile2187Val variant is likely to be benign.
Mendelics RCV000490254 SCV001136852 benign Usher syndrome, type 2C 2019-05-28 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000490254 SCV001318528 likely benign Usher syndrome, type 2C 2018-01-12 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.

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