ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.3045C>G (p.His1015Gln) (rs541918040)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000156761 SCV000206482 uncertain significance not specified 2014-09-04 criteria provided, single submitter clinical testing The His1015Gln variant in USH2A has not been previously reported in individuals with hearing loss and was absent from large population studies. Computational pr ediction tools and conservation analyses do not provide strong support for or ag ainst an impact to the protein. In summary, the clinical significance of the His 1015Gln variant is uncertain.
Illumina Clinical Services Laboratory,Illumina RCV000378937 SCV000354142 uncertain significance Usher syndrome, type 2A 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 Clinical Services Laboratory,Illumina RCV000286781 SCV000354143 uncertain significance Retinitis pigmentosa 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.
Counsyl RCV000667957 SCV000792489 uncertain significance Usher syndrome, type 2A; Retinitis pigmentosa 39 2017-06-26 criteria provided, single submitter clinical testing
Invitae RCV001070473 SCV001235719 uncertain significance not provided 2019-10-25 criteria provided, single submitter clinical testing This sequence change replaces histidine with glutamine at codon 1015 of the USH2A protein (p.His1015Gln). The histidine residue is moderately conserved and there is a small physicochemical difference between histidine and glutamine. This variant is present in population databases (rs541918040, ExAC 0.01%). This variant has been observed in an individual affected with retinitis pigmentosa (PMID: 26927203). ClinVar contains an entry for this variant (Variation ID: 179958). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Human Genetics - Radboudumc,Radboudumc RCV000678650 SCV000804741 uncertain significance Retinitis pigmentosa 39 2016-09-01 no assertion criteria provided clinical testing

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