ClinVar Miner

Submissions for variant NM_144612.6(LOXHD1):c.4031G>T (p.Cys1344Phe) (rs368870055)

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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 RCV000155146 SCV000204832 uncertain significance not specified 2014-01-02 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The Cys1344Phe vari ant in LOXHD1 has now been identified by our laboratory in three individuals wit h hearing loss, all with alternate explanations for their hearing loss. This var iant has also been identified in 0.09% (3/3182) of the European American populat ion by the NHLBI Exome Sequencing Project; however, this frequency is not high e nough to rule out a pathogenic role, particularly for a recessive disorder. Comp utational analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to t he protein. In summary, the clinical significance of this variant cannot be dete rmined with certainty at this time. However, based on only being identified in a ffected individuals with an alternative explanation of their hearing loss and id entification in the general population, we would lean towards a more likely beni gn role.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000155146 SCV000707020 benign not specified 2017-03-30 criteria provided, single submitter clinical testing
Invitae RCV000908734 SCV001053512 benign not provided 2019-12-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001124116 SCV001283036 uncertain significance Deafness, autosomal recessive 77 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

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