ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.3503G>A (p.Arg1168Gln) (rs797044516)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000623408 SCV000741576 pathogenic Inborn genetic diseases 2016-06-23 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: POSITIVE: Relevant Alteration(s) Detected
Counsyl RCV000675162 SCV000800779 likely pathogenic Deafness, autosomal recessive 2; Usher syndrome, type 1 2017-08-03 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000156269 SCV000205986 uncertain significance not specified 2014-01-03 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Pathogenic. The 3503G>A (Ar g1168Gln) variant in MYO7A has not been previously reported in individuals with hearing loss. Data from large population studies is insufficient to assess the f requency of this variant. This variant is located in the last base of exon 27 in the major transcript (NM_000260.3) of MYO7A, which is part of the conserved 5? splice region of intron 27. Computational tools suggest an impact to splicing; h owever, this information is not predictive enough to determine pathogenicity. Ho wever, a different variant at the same nucleotide (3503G>C, Arg1168Pro) has been previously described in an individual with Usher syndrome who was compound hete rozygous for a second pathogenic variant (Jaijo 2006). Functional studies demons trated that the 3503G>C variant led to skipping of exon 27 (Le Guedard-Mereuze 2 010), suggesting that variants that alter the c.3503G nucleotide cause abnormal splicing. In summary, the clinical significance of this variant cannot be determ ined with certainty; however based upon its location within the splice consensus sequence and its predicted impact on splicing, we would lean towards a more lik ely pathogenic role.

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