ClinVar Miner

Submissions for variant NM_144612.6(LOXHD1):c.2251C>T (p.Arg751Trp) (rs376539851)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000041201 SCV000064892 uncertain significance not specified 2018-04-04 criteria provided, single submitter clinical testing The p.Arg751Trp variant in LOXHD1 has been previously identified by our laborat ory in three individuals congenital hearing loss; however a second variant in tr ans (on the other copy of the gene) was not identified in any of the individuals . This variant has been identified in 0.13% (11/8522) of Ashkenazi Jewish chromo somes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.o rg; dbSNP rs376539851). Although this variant has been seen in the general popul ation, its frequency is not high enough to rule out a pathogenic role. The p.Arg 751Trp variant has been seen in the heterozygous state in one individual with la te-onset Fuchs corneal dystrophy (FCD); however the hearing status was not repor ted (Riazuddin 2012). This variant's association with FCD has not been reported in other affected individuals, which, given the frequency in the general populat ion and presumed autosomal dominant inheritance pattern of FCD, does not support a strong correlation between this variant and FCD. Computational prediction too ls and conservation analysis do not provide strong support for or against an imp act to the protein. In summary, the clinical significance of the p.Arg751Trp var iant is uncertain. ACMG/AMP Criteria applied: None.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000727175 SCV000706347 uncertain significance not provided 2017-02-08 criteria provided, single submitter clinical testing
Counsyl RCV000668714 SCV000793359 uncertain significance Deafness, autosomal recessive 77 2017-08-15 criteria provided, single submitter clinical testing

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