NM_001008212.2(OPTN):c.493C>T (p.Gln165Ter) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 18, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV003103163.3

Allele description [Variation Report for NM_001008212.2(OPTN):c.493C>T (p.Gln165Ter)]

NM_001008212.2(OPTN):c.493C>T (p.Gln165Ter)

Gene:

OPTN:optineurin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10p13

Genomic location:

Preferred name:

NM_001008212.2(OPTN):c.493C>T (p.Gln165Ter)

HGVS:

NC_000010.11:g.13112576C>T
NG_012876.1:g.17495C>T
NM_001008211.1:c.493C>T
NM_001008212.2:c.493C>TMANE SELECT
NM_001008213.1:c.493C>T
NM_021980.4:c.493C>T
NP_001008212.1:p.Gln165Ter
NP_001008213.1:p.Gln165Ter
NP_001008214.1:p.Gln165Ter
NP_068815.2:p.Gln165Ter
NC_000010.10:g.13154576C>T

Protein change:

Q165*

Molecular consequence:

NM_001008211.1:c.493C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001008212.2:c.493C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001008213.1:c.493C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_021980.4:c.493C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Primary open angle glaucoma (POAG)
Synonyms:: OPTN-related open angle glaucoma
Identifiers:: MONDO: MONDO:0100553; MedGen: C0339573; OMIM: 137760

Name:: Amyotrophic lateral sclerosis type 12 (ALS12)
Synonyms:: AMYOTROPHIC LATERAL SCLEROSIS 12 WITH OR WITHOUT FRONTOTEMPORAL DEMENTIA
Identifiers:: MONDO: MONDO:0013264; MedGen: C3150692; Orphanet: 803; OMIM: 613435

Name:: Glaucoma 1, open angle, E
Identifiers:: MedGen: C1842026

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003274663	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 18, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 20428114, 26203661, 21802176, 21852022, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003274663

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 18, 2022)

germline

clinical testing

PubMed (5)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations of optineurin in amyotrophic lateral sclerosis.

Maruyama H, Morino H, Ito H, Izumi Y, Kato H, Watanabe Y, Kinoshita Y, Kamada M, Nodera H, Suzuki H, Komure O, Matsuura S, Kobatake K, Morimoto N, Abe K, Suzuki N, Aoki M, Kawata A, Hirai T, Kato T, Ogasawara K, Hirano A, et al.

Nature. 2010 May 13;465(7295):223-6. doi: 10.1038/nature08971. Epub 2010 Apr 28.

PubMed [citation]

PMID:: 20428114

A Dutch family with autosomal recessively inherited lower motor neuron predominant motor neuron disease due to optineurin mutations.

Beeldman E, van der Kooi AJ, de Visser M, van Maarle MC, van Ruissen F, Baas F.

Amyotroph Lateral Scler Frontotemporal Degener. 2015;16(5-6):410-1. doi: 10.3109/21678421.2015.1066821. Epub 2015 Jul 23.

PubMed [citation]

PMID:: 26203661

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003274663.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This variant is present in population databases (no rsID available, gnomAD 0.002%). This sequence change creates a premature translational stop signal (p.Gln165*) in the OPTN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in OPTN are known to be pathogenic (PMID: 20428114). For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with autosomal recessive amyotrophic lateral sclerosis (PMID: 26203661). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant has been reported in individual(s) with autosomal dominant amyotrophic lateral sclerosis (PMID: 21802176, 21852022); however, the role of the variant in this condition is currently unclear.

#	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: Jan 4, 2025

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