Submissions for variant NM_001384474.1(LOXHD1):c.1617G>A (p.Met539Ile)

gnomAD frequency: 0.00178  dbSNP: rs143142227

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000150986	SCV000198672	benign	not specified	2016-06-21	criteria provided, single submitter	clinical testing	p.Met539Ile in exon 12 of LOXHD1: This variant is not expected to have clinical significance because it has been identified in 0.7% (20/2898) of African chromos omes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs143142227)
Eurofins Ntd Llc (ga)	RCV000150986	SCV000343161	likely benign	not specified	2016-08-12	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000385343	SCV000408770	uncertain significance	Autosomal recessive nonsyndromic hearing loss 77	2018-01-13	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000900853	SCV001045196	likely benign	not provided	2024-12-16	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004019812	SCV004897305	uncertain significance	Inborn genetic diseases	2022-01-10	criteria provided, single submitter	clinical testing	The c.1617G>A (p.M539I) alteration is located in exon 12 (coding exon 12) of the LOXHD1 gene. This alteration results from a G to A substitution at nucleotide position 1617, causing the methionine (M) at amino acid position 539 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc.	RCV000385343	SCV002086330	likely benign	Autosomal recessive nonsyndromic hearing loss 77	2019-11-22	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003952718	SCV004778227	likely benign	LOXHD1-related disorder	2021-12-01	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).