ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.4018G>A (p.Ala1340Thr) (rs376291076)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000665055 SCV000789114 uncertain significance Deafness, autosomal recessive 2; Usher syndrome, type 1 2017-01-10 criteria provided, single submitter clinical testing
GeneDx RCV000421377 SCV000513834 uncertain significance not provided 2017-10-04 criteria provided, single submitter clinical testing The A1340T variant has been published previously in association with Usher syndrome and hearing impairment (Vozzi et al., 2011; Kimberling et al., 2010). However, no other MYO7A variants were detected in the patients in these studies. The A1340T variant was not observed at any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species; however, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000825981 SCV000967469 uncertain significance not specified 2018-12-13 criteria provided, single submitter clinical testing The p.Ala1340Thr variant in MYO7A has been previously reported in at least 2 ind ividuals with hearing loss or Usher syndrome, however a variant affecting the re maining copy of MYO7A was not identified (Cremers 2007, Kimberling 2010, Vozzi 2 011). This variant has also been identified in 0.13% (14/10342) of Ashkenazi Jew ish chromosomes by gnomAD (http://gnomad.broadinstitute.org). Computational pred iction tools and conservation analysis do not provide strong support for or agai nst an impact to the protein. In summary, the clinical significance of this vari ant is uncertain. ACMG/AMP Criteria applied: BS1_Supporting.

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