ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.1132C>T (p.Arg378Cys) (rs199818783)

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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 RCV000036039 SCV000059691 uncertain significance not specified 2013-05-07 criteria provided, single submitter clinical testing The Arg378Cys variant in MYO7A has been previously identified by our laboratory in one individual with Usher syndrome; however, the variant was heterozygous in this individual and a second MYO7A variant was not detected (LMM unpublished da ta). It has also been identified in 0.04% (3/8378) of European American chromos omes by the NHLBI Exome sequencing project (http://evs.gs.washington.edu/EVS; db SNP rs199818783). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. Computational a nalyses (biochemical, amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein . In summary, additional information is needed to determine the clinical signifi cance of this variant.
Counsyl RCV000665432 SCV000789556 uncertain significance Deafness, autosomal recessive 2; Usher syndrome type 1 2017-02-07 criteria provided, single submitter clinical testing
Blueprint Genetics RCV001075067 SCV001240678 uncertain significance Retinal dystrophy 2018-07-02 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001111945 SCV001269555 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.
Illumina Clinical Services Laboratory,Illumina RCV001111946 SCV001269556 likely benign 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 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 RCV001111947 SCV001269557 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.
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001199110 SCV001370105 uncertain significance Neurodevelopmental disorder 2019-03-24 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. The available evidence on this varinat's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PM2. This variant was detected in heterozygous state.
Invitae RCV001247583 SCV001421013 uncertain significance not provided 2019-10-21 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 378 of the MYO7A protein (p.Arg378Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs199818783, 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: 43135). 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: "Deleterious"; PolyPhen-2: "Probably 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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