ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.2886G>C (p.Gln962His) (rs200641606)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000036098 SCV000059750 likely benign not specified 2016-06-09 criteria provided, single submitter clinical testing p.Gln962His in exon 23 of MYO7A: This variant is not expected to have clinical s ignificance because it has been identified in 0.3% (39/15796) of South Asian chr omosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.o rg; dbSNP rs200641606). Although this variant has been reported in two individu als with hearing loss, in one individual two other pathogenic or likely pathogen ic variants were identified (LeQuesne Stabej 2012), and in the other individual a variant affecting the remaining copy of MYO7A was not identified. Therefore, given the frequency of this variant, it is likely benign.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000585012 SCV000227997 uncertain significance not provided 2014-12-19 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000585012 SCV000692720 uncertain significance not provided 2017-09-01 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000585012 SCV000884213 uncertain significance not provided 2017-09-16 criteria provided, single submitter clinical testing The p.Gln962His variant (rs200641606) has been reported in one individual with a clinical diagnosis of Usher syndrome (Le Quesne Stabej 2012); however, inheritance and specific clinical information were not reported for this individual. The p.Gln962His variant is listed in the Genome Aggregation Database (gnomAD) browser with an overall allele frequency of 0.068% (identified in 187 out of 276,178 chromosomes; 0 homozygotes), and is classified as a variant of uncertain significance in ClinVar (Variant ID: 43194). The glutamine at codon 962 is moderately conserved considering 13 species (Alamut software v2.9.0), and computational analyses suggest that this variant affects the MYO7A protein structure/function (SIFT: damaging, PolyPhen2: possibly damaging, MutationTaster: disease causing). However, based on the available information, the clinical significance of the p.Gln962His variant cannot be determined with certainty.
Athena Diagnostics Inc RCV000585012 SCV001144662 uncertain significance not provided 2019-03-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001114199 SCV001272050 likely benign Deafness, autosomal dominant 11 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 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.
Illumina Clinical Services Laboratory,Illumina RCV001114200 SCV001272051 uncertain significance Usher syndrome type 1 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 RCV001114201 SCV001272052 uncertain significance Deafness, autosomal recessive 2 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.
Invitae RCV000585012 SCV001421595 uncertain significance not provided 2019-12-31 criteria provided, single submitter clinical testing This sequence change replaces glutamine with histidine at codon 962 of the MYO7A protein (p.Gln962His). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and histidine. This variant is present in population databases (rs200641606, ExAC 0.2%). This variant has not been reported in the literature in individuals with MYO7A-related conditions. ClinVar contains an entry for this variant (Variation ID: 43194). 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"). 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.

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