ClinVar Miner

Submissions for variant NM_001384474.1(LOXHD1):c.5731G>A (p.Gly1911Arg)

gnomAD frequency: 0.00001  dbSNP: rs780560784
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000605343 SCV000712142 uncertain significance not specified 2016-06-02 criteria provided, single submitter clinical testing The p.Gly1849Arg variant in LOXHD1 has not been previously reported in individua ls with hearing loss. This variant has been identified in 1/7912 South Asian chr omosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.o rg; dbSNP rs780560784); however, its frequency is not high enough to rule out a pathogenic role. Computational prediction tools and conservation analyses sugges t that this variant may impact the protein, though this information is not predi ctive enough to determine pathogenicity. In summary, the clinical significance o f the p.Gly1849Arg variant is uncertain.
3billion RCV001275163 SCV002058798 uncertain significance Autosomal recessive nonsyndromic hearing loss 77 2022-01-03 criteria provided, single submitter clinical testing The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000013, PM2_M). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.872, 3CNET: 0.919, PP3_P). Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline.
Centre for Clinical Genetics and Genomic Diagnostics, Zealand University Hospital RCV004721472 SCV005328483 pathogenic not provided 2024-08-19 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV001275163 SCV005652037 likely pathogenic Autosomal recessive nonsyndromic hearing loss 77 2024-01-04 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV004721472 SCV005813060 likely pathogenic not provided 2024-03-11 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1849 of the LOXHD1 protein (p.Gly1849Arg). This variant is present in population databases (rs780560784, gnomAD 0.01%). This missense change has been observed in individual(s) with deafness (PMID: 28984810, 35711932). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 505057). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Natera, Inc. RCV001275163 SCV001460008 uncertain significance Autosomal recessive nonsyndromic hearing loss 77 2020-09-16 no assertion criteria provided clinical testing

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