ClinVar Miner

Submissions for variant NM_016239.4(MYO15A):c.9303+1G>T

dbSNP: rs876657708
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV001818513 SCV002064509 likely pathogenic not provided 2021-11-18 criteria provided, single submitter clinical testing DNA sequence analysis of the MYO15A gene demonstrated a sequence change in the canonical splice donor site of intron 55, c.9303+1G>T. This sequence change is predicted to disrupt the canonical splice donor site, and affect normal splicing of exon 55. The c.9303+1G>T change has not been previously described in individual with MYO15A-related disorder. This sequence change has not been described in the gnomAD population database. Collectively, this evidence suggests c.9303+1G>T is likely pathogenic, however, functional studies have not been performed to prove this conclusively.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000218653 SCV000271416 pathogenic Rare genetic deafness 2015-06-16 criteria provided, single submitter clinical testing The c.9303+1G>T variant in MYO15A has not been previously reported in individual s with hearing loss and was absent from large population studies. This variant o ccurs in the invariant region (+/- 1/2) of the splice consensus sequence and is predicted to cause altered splicing leading to an abnormal or absent protein. Lo ss-of-function variants in the MYO15A gene are an established disease mechanism for autosomal recessive hearing loss. In summary, this variant meets our criteri a to be classified as pathogenic for hearing loss in an autosomal recessive mann er (www.partners.org/personalizedmedicine/lmm), based on the predicted impact of the variant.

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