ClinVar Miner

Submissions for variant NM_144612.6(LOXHD1):c.1730T>G (p.Leu577Arg) (rs727503147)

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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,Partners HealthCare Personalized Medicine RCV000150985 SCV000198671 uncertain significance not specified 2013-10-11 criteria provided, single submitter clinical testing The Leu577Arg variant in LOXHD1 has been reported in one individual with hearing loss who did not carry a second variant in LOXHD1 (Shearer 2013). The variant h as not been reported in large population databases including the 1000 Genome Pro ject and the NHLBI Exome Variant Server (http://evs.gs.washington.edu/EVS/). Com putational analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. In summary, additional data is needed to determine the clinical sig nificance of this variant.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000727380 SCV000708017 uncertain significance not provided 2017-05-01 criteria provided, single submitter clinical testing
Counsyl RCV000669854 SCV000794646 uncertain significance Deafness, autosomal recessive 77 2017-10-12 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000669854 SCV000915319 uncertain significance Deafness, autosomal recessive 77 2017-08-10 criteria provided, single submitter clinical testing The LOXHD1 c.1730T>G (p.Leu577Arg) missense variant has been reported in at least three studies in which it is found in three individuals with congenital or childhood onset severe hearing loss, including in one in a compound heterozygous state with a frameshift variant, one in a compound heterozygous state with two additional LOXHD1 variants, the conformation of which was not determined, and one in a heterozygous state along with four additional variants of undetermined pathogenicity in four hearing loss-associated genes (Shearer et al. 2013; Sloan-Heggen et al. 2016; Zazo Seco et al. 2017). Control data are unavailable for the p.Leu577Arg variant, which is reported at a frequency of 0.00029 in the European (non-Finnish) population of Genome Aggregation Database. Based on the evidence, the p.Leu577Arg variant is classified as a variant of unknown significance but suspicious for pathogenicity for autosomal recessive nonsyndromic hearing loss. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

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