ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.803A>G (p.Lys268Arg) (rs184866544)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000155225 SCV000204911 likely benign not specified 2015-05-17 criteria provided, single submitter clinical testing p.Lys268Arg in exon 8 of MYO7A: This variant was reported in one individual with Usher syndrome type 2 but did not segregate in an affected sibling (Bonnet 2011 ). In addition, this variant was identified in 0.2% (100/53924) of European chro mosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.or g; dbSNP rs184866544). Furthermore, the lysine (Lys) residue at this position is not conserved in mammals and evolutionary distant species with two mammals, hor se and dolphin, having an arginine (Arg) at this position. In summary, this vari ant is not expected to have clinical significance based on lack of segregation w ith disease, the frequency of the variant in the general population, and conserv ation data.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000724234 SCV000232497 uncertain significance not provided 2014-11-07 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000724234 SCV001148372 uncertain significance not provided 2019-08-01 criteria provided, single submitter clinical testing
Invitae RCV000724234 SCV001209819 uncertain significance not provided 2019-12-30 criteria provided, single submitter clinical testing This sequence change replaces lysine with arginine at codon 268 of the MYO7A protein (p.Lys268Arg). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and arginine. This variant is present in population databases (rs184866544, 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: 178477). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Illumina Clinical Services Laboratory,Illumina RCV001112307 SCV001269958 likely benign Deafness, autosomal dominant 11 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Clinical Services Laboratory,Illumina RCV001112308 SCV001269959 uncertain significance Deafness, autosomal recessive 2 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001112309 SCV001269960 uncertain significance Usher syndrome type 1 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
GeneDx RCV000724234 SCV001825754 uncertain significance not provided 2020-10-28 criteria provided, single submitter clinical testing Reported in published literature in an individual with Usher syndrome who was also heterozygous for a pathogenic variant in the USH2A gene, but was not present in an affected sibling (Bonnet et al., 2011); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 30245029, 21569298, 25262649)

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