Submissions for variant NM_001384474.1(LOXHD1):c.977A>G (p.Asn326Ser)

gnomAD frequency: 0.00020  dbSNP: rs188528174

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000155732	SCV000205442	likely benign	not specified	2016-05-21	criteria provided, single submitter	clinical testing	p.Asn326Ser in exon 8 of LOXHD1: This variant is not expected to have clinical s ignificance due to frequency data, conservation data, and previous reports. It has been identified in 0.9% (6/648) of East Asian chromosomes by the Exome Aggre gation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs188528174). Th e asparagine (Asn) at position 326 is not conserved in mammals or evolutionary d istant species, with two mammals (pig and armadillo) having a serine (Ser), supp orting that a change at this position may be tolerated. In addition, this varia nt has been previously reported in an individual with hearing loss by our labora tory who had an alternate explanation of the hearing loss identified. Therefor e, this data collectively suggests that the p.Asn326Ser variant is likely benign .
Labcorp Genetics (formerly Invitae), Labcorp	RCV000901310	SCV001045675	likely benign	not provided	2024-03-25	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001125426	SCV001284494	uncertain significance	Autosomal recessive nonsyndromic hearing loss 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.
GeneDx	RCV000901310	SCV001820134	uncertain significance	not provided	2023-07-01	criteria provided, single submitter	clinical testing	Observed with a second LOXHD1 variant in a patient with deafness, but it is not known whether the variants occurred on the same (in cis) or on different (in trans) chromosomes (Li et al., 2021); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 33724713, 25668207)
PreventionGenetics, part of Exact Sciences	RCV004751303	SCV005353861	likely benign	LOXHD1-related disorder	2024-07-13	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).