ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.4450C>T (p.Leu1484Phe) (rs200416912)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000664783 SCV000788795 uncertain significance Deafness, autosomal recessive 2; Usher syndrome, type 1 2016-12-15 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000778344 SCV000914544 uncertain significance Usher syndrome, type 1 2017-11-21 criteria provided, single submitter clinical testing The MYO7A gene is one of at least nine genes in which variants are known to cause Usher syndrome and this gene is associated with Usher syndrome type 1 (USH1) and Usher syndrome type 2 (USH2). The c.4450C>T (p.Leu1484Phe) variant has been reported in a compound heterozygous state with a second missense variant in a Spanish individual with USH1 (Jaijo et al. 2006). The p.Leu1484Phe variant was shown to be absent from 100 control chromosomes and is reported at a frequency of 0.000360 in the European American population of the Exome Sequencing Project. It is predicted to affect the structure of the protein as it occurs in the folding core of the FERM domain (Wu et al. 2011); however, functional studies of its effects have not been conducted. The evidence for this variant is limited. The p.Leu1484Phe variant is therefore classified as a variant of unknown significance but suspicious for pathogenicity for Usher syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000036145 SCV000059797 uncertain significance not specified 2013-03-11 criteria provided, single submitter clinical testing The Leu1484Phe variant in MYO7A has been reported in one individual with the cli nical features of Usher syndome type I who carried a second missense variant in MYO7A (Jaijo 2006), but has not been identified in any additional affected indiv iduals. However, this variant has been seen in 0.04% (3/8342) of European Americ an chromosomes in a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs200316912); though this frequency is not h igh enough to rule out a pathogenic rule. Computational analyses (biochemical am ino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provid e strong support for or against an impact to the protein. In summary, additional information is needed to determine the clinical significance of this variant.

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