ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.689C>T (p.Ala230Val) (rs797044512)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000155771 SCV000205482 pathogenic Rare genetic deafness 2013-06-11 criteria provided, single submitter clinical testing The Ala230Val variant in MYO7A has been reported in a large Italian pedigree aff ected with nonsyndromic post-lingual progressive hearing loss showing autosomal dominant inheritance(Di Leva 2006). The variant co-segregated with hearing loss in several affected family members, and was not identified in unaffected family members or in 200 ethnically matched control chromosomes (Di Leva 2006). In addi tion, this variant was not identified in large population studies. Furthermore, the alanine (Ala) residue at position 230 is located in the conserved motor doma in of the MYO7A protein. Missense variants in this region of the protein have be en associated with autosomal dominant hearing loss. In summary, this variant mee ts our criteria to be classified as pathogenic ( b ased upon segregation analysis.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000506187 SCV000604428 likely pathogenic not specified 2016-10-12 criteria provided, single submitter clinical testing
Laboratory of Prof. Karen Avraham,Tel Aviv University RCV000225087 SCV000281977 pathogenic Deafness, autosomal dominant 11 2016-02-16 no assertion criteria provided research childhood onset, progressive HL, also myopia
New York Genome Center RCV001254945 SCV001431027 likely pathogenic Bilateral sensorineural hearing impairment 2020-01-20 no assertion criteria provided clinical testing The p.Ala230Val missense variant has been reported to co-segregate with autosomal dominant non-syndromic progressive hearing loss in a large Italian family [PMID: 16449806]. The p.Ala230Val variant has also been reported in an unrelated 5-year old boy affected with moderate bilateral hearing loss [PMID: 28802369]. The variant is absent from the gnomAD database indicating that it is an extremely rare allele in the general population. The p.Ala230Val variant is predicted deleterious by various in silico prediction tools. The affected alanine residue is evolutionarily conserved and is located within the functionally important motor domain of MYO7A molecule. Missense variants in this region of the protein have been associated with autosomal dominant hearing loss. Based on the available evidence, the p.Ala230Val missense variant in the MYO7A gene is assessed as likely pathogenic.

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