ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.6247G>A (p.Ala2083Thr) (rs41298759)

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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 RCV000155244 SCV000204930 likely benign not specified 2020-01-15 criteria provided, single submitter clinical testing The p.Ala2083Thr variant in MYO7A is classified as likely benign because it has been identified in 0.2% (18/10348) of Ashkenazi Jewish chromosomes by gnomAD (http://gnomad.broadinstitute.org), and computational prediction tools and conservation analysis suggest that this variant may not impact the protein. ACMG/AMP criteria applied: BS1_Supporting, BP4.
Illumina Clinical Services Laboratory,Illumina RCV000290561 SCV000374515 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 RCV001089552 SCV000374516 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 RCV000386123 SCV000374517 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.
Fulgent Genetics,Fulgent Genetics RCV000765019 SCV000896203 uncertain significance Deafness, autosomal dominant 11; Deafness, autosomal recessive 2; Usher syndrome type 1 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV001034255 SCV001197587 likely benign not provided 2019-12-23 criteria provided, single submitter clinical testing
Victorian Clinical Genetics Services,Murdoch Childrens Research Institute RCV001089552 SCV001244763 uncertain significance Deafness, autosomal recessive 2 2018-06-26 criteria provided, single submitter clinical testing A heterozygous missense variant, NM_000260.3(MYO7A):c.6247G>A, has been identified in exon 46 of 49 of the MYO7A gene. The variant is predicted to result in a minor amino acid change from alanine to threonine at position 2083 of the protein (NP_000251.3(MYO7A):p.(Ala2083Thr)). The alanine residue at this position has high conservation (100 vertebrates, UCSC), and is located within the FERM functional domain. In silico predictions of pathogenicity for this variant are conflicting (Polyphen, SIFT, CADD, Mutation Taster). The variant is present in the gnomAD database at a frequency of 0.036% (99 heterozygotes, 1 homozygote). The variant has been previously described as a Variant of Unknown Significance (ClinVar, Deafness Variation Database). Based on the information available at the time of curation, this variant has been classified as a VARIANT of UNCERTAIN SIGNIFICANCE (VUS) with LOW CLINICAL RELEVANCE.

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