ClinVar Miner

Submissions for variant NM_016239.4(MYO15A):c.7893+1G>A

gnomAD frequency: 0.00001  dbSNP: rs727503316
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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, Mass General Brigham Personalized Medicine RCV000151411 SCV000199423 pathogenic Rare genetic deafness 2013-05-21 criteria provided, single submitter clinical testing The 7893+1G>A variant in MYO15A has not been reported in affected individuals or in large population studies. This variant occurs 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. Loss of function is an established dis ease mechanism for MYO15A. Therefore, this variant meets our criteria to be clas sified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV001723714 SCV002288357 likely pathogenic not provided 2023-06-03 criteria provided, single submitter clinical testing Disruption of this splice site has been observed in individual(s) with clinical features of deafness (PMID: 27068579). ClinVar contains an entry for this variant (Variation ID: 164552). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant is present in population databases (rs727503316, gnomAD 0.005%). This sequence change affects a donor splice site in intron 41 of the MYO15A gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MYO15A are known to be pathogenic (PMID: 17546645).
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV001723714 SCV001954053 pathogenic not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001723714 SCV001969133 pathogenic not provided no assertion criteria provided clinical testing

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