ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.2798G>A (p.Arg933His) (rs201489714)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000216662 SCV000272151 uncertain significance not specified 2017-02-28 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Arg933His var iant in MYO7A has been previously reported by our laboratory in one individual w ith Usher syndrome due to an alternate genetic etiology. It has also been identi fied in 0.04% (24/59080) of European chromosomes by the Exome Aggregation Consor tium (ExAC, http://exac.broadinstitute.org; dbSNP rs201489714). Although this va riant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. Computational prediction tools and conservation analyses suggest that the p.Arg933His variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary , while the clinical significance of the p.Arg933His variant is uncertain, avail able data suggest that it is more likely to be benign.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000488266 SCV000339674 uncertain significance not provided 2016-02-12 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000488266 SCV000574901 uncertain significance not provided 2016-12-01 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000488266 SCV000884216 uncertain significance not provided 2018-04-18 criteria provided, single submitter clinical testing The MYO7A c.2798G>A p.Arg933His variant (rs201489714, ClinVar variant ID 229004) was detected in a family with Usher syndrome IC; however, a pathogenic variant in the USH1C gene segregated with disease in this family, while the MYO7A p.Arg933His variant was found in one affected and one unaffected individual, making it unclear whether or not the latter variant contributed to disease (Umrigar 2017). This variant is listed in the genome Aggregation Database (gnomAD) with a non-Finnish European population frequency of 0.05% (identified on 59 out of 125,704 chromosomes). The arginine at position 933 is moderately conserved, considering 13 species, and computational analyses of the effects of the p.Arg933His variant on protein structure and function do not predict a deleterious effect (SIFT: tolerated, PolyPhen-2: benign). Based on the available information, the clinical significance of the p.Arg933His variant cannot be determined with certainty.
Illumina Clinical Services Laboratory,Illumina RCV001112846 SCV001270550 uncertain significance Deafness, autosomal dominant 11 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, 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 RCV001112847 SCV001270551 uncertain significance Usher syndrome type 1 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, 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 RCV001112848 SCV001270552 uncertain significance Deafness, autosomal recessive 2 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, 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.

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