NM_001384474.1(LOXHD1):c.2497C>T (p.Arg833Ter) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Aug 4, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000512767.10

Allele description [Variation Report for NM_001384474.1(LOXHD1):c.2497C>T (p.Arg833Ter)]

NM_001384474.1(LOXHD1):c.2497C>T (p.Arg833Ter)

Gene:

LOXHD1:lipoxygenase homology PLAT domains 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

18q21.1

Genomic location:

Preferred name:

NM_001384474.1(LOXHD1):c.2497C>T (p.Arg833Ter)

HGVS:

NC_000018.10:g.46563166G>A
NG_016646.2:g.98868C>T
NM_001384474.1:c.2497C>TMANE SELECT
NM_144612.7:c.2497C>T
NP_001371403.1:p.Arg833Ter
NP_653213.6:p.Arg833Ter
NP_653213.6:p.Arg833Ter
NC_000018.9:g.44143129G>A
NM_144612.6:c.2497C>T
c.2497C>T
p.Arg833X

Protein change:

R833*

Links:

dbSNP: rs188119157

NCBI 1000 Genomes Browser:

rs188119157

Molecular consequence:

NM_001384474.1:c.2497C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_144612.7:c.2497C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000608858	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (Praxis fuer Humangenetik Tuebingen - Variant Classification Criteria)	Likely pathogenic (Mar 31, 2017)	germline	clinical testing	Citation Link,
SCV001218657	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 4, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 19732867, 21465660, 25792669, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000608858

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(Praxis fuer Humangenetik Tuebingen - Variant Classification Criteria)

Likely pathogenic
(Mar 31, 2017)

germline

clinical testing

Citation Link,

SCV001218657

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 4, 2024)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in LOXHD1, an evolutionarily conserved stereociliary protein, disrupt hair cell function in mice and cause progressive hearing loss in humans.

Grillet N, Schwander M, Hildebrand MS, Sczaniecka A, Kolatkar A, Velasco J, Webster JA, Kahrizi K, Najmabadi H, Kimberling WJ, Stephan D, Bahlo M, Wiltshire T, Tarantino LM, Kuhn P, Smith RJ, Müller U.

Am J Hum Genet. 2009 Sep;85(3):328-37. doi: 10.1016/j.ajhg.2009.07.017.

PubMed [citation]

PMID:: 19732867
PMCID:: PMC2771534

A deleterious mutation in the LOXHD1 gene causes autosomal recessive hearing loss in Ashkenazi Jews.

Edvardson S, Jalas C, Shaag A, Zenvirt S, Landau C, Lerer I, Elpeleg O.

Am J Med Genet A. 2011 May;155A(5):1170-2. doi: 10.1002/ajmg.a.33972. Epub 2011 Apr 4.

PubMed [citation]

PMID:: 21465660

See all PubMed Citations (4)

Details of each submission

From CeGaT Center for Human Genetics Tuebingen, SCV000608858.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001218657.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Arg833*) in the LOXHD1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LOXHD1 are known to be pathogenic (PMID: 19732867, 21465660, 25792669). This variant is present in population databases (rs188119157, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with LOXHD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 47930). For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 28, 2025

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