ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.2558G>A (p.Arg853His) (rs111033437)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Hearing Loss Variant Curation Expert Panel RCV001004783 SCV001164267 likely pathogenic Nonsyndromic hearing loss and deafness 2019-10-29 reviewed by expert panel curation The c.2558G>A (p.Arg853His) variant in MYO7A was present in 0.001549% (1/64572) of non-Finnish European chromosomes in gnomAD, which is a low enough frequency to apply PM2 based on the thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal dominant hearing loss (PM2; This variant has been identified in at least 3 probands with ADNSHL (PS4_Supporting; PMID: 23804846, 26969326; LMM unpublished data, SCV000059742.6). The p.Arg853His variant segregated with hearing loss in 10 affected family members (PP1_Strong; Tokyo Medical Center unpublished data, SCV000882720.1). The REVEL computational prediction analysis tool produced a score of 0.741, which is above the threshold necessary to apply PP3. In summary, this variant meets criteria to be classified as likely pathogenic for autosomal dominant hearing loss. ACMG/AMP Criteria applied, as specified by the Hearing Loss Expert Panel: PP1_Strong, PM2, PP3, PS4_Supporting.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000036090 SCV000059742 uncertain significance not specified 2013-11-03 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Pathogenic. The Arg853His v ariant in MYO7A has been reported in a German family with autosomal dominant pro gressive hearing loss where it was shown to segregate with hearing loss in 4 aff ected family members (Bolz 2004). An impact to protein function was proposed by the authors based upon an in vitro assay. The variant has also been reported in another individual with hearing loss; however phenotypic data for this individu al (including a likely inheritance pattern) was not provided (Shearer 2013). Dat a from large population studies is insufficient, and computational analyses (bio chemical 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 fully assess the clinical significance of the Arg853His variant.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000724679 SCV000227756 uncertain significance not provided 2015-03-20 criteria provided, single submitter clinical testing
National Institute of Sensory Organs,National Hospital Organization Tokyo Medical Center RCV000791456 SCV000882720 likely pathogenic Deafness, autosomal dominant 11 2018-04-24 criteria provided, single submitter research The variant was identified using linkage analysis from a pedigree showing hearing loss for 5-generations. The locus between rs1462224 and rs591804 showed HLOD score >3.0. Variants of the two deafness genes (CABP2 and LRTOMT) on the locus were not cosegregated with hearing loss. MYO7A was mapped on the adjacent region, where the LOD score was >2.0.
Fulgent Genetics,Fulgent Genetics RCV000765015 SCV000896199 uncertain significance Deafness, autosomal dominant 11; Deafness, autosomal recessive 2; Usher syndrome type 1 2018-10-31 criteria provided, single submitter clinical testing
Knight Diagnostic Laboratories, Oregon Health and Sciences University RCV000724679 SCV001448934 likely pathogenic not provided 2019-11-27 criteria provided, single submitter clinical testing

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