NM_001008212.2(OPTN):c.1195G>T (p.Glu399Ter) 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:
RCV002601689.3

Allele description [Variation Report for NM_001008212.2(OPTN):c.1195G>T (p.Glu399Ter)]

NM_001008212.2(OPTN):c.1195G>T (p.Glu399Ter)

Gene:
OPTN:optineurin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
10p13
Genomic location:
Preferred name:
NM_001008212.2(OPTN):c.1195G>T (p.Glu399Ter)
HGVS:
  • NC_000010.11:g.13125992G>T
  • NG_012876.1:g.30911G>T
  • NM_001008211.1:c.1195G>T
  • NM_001008212.2:c.1195G>TMANE SELECT
  • NM_001008213.1:c.1195G>T
  • NM_021980.4:c.1195G>T
  • NP_001008212.1:p.Glu399Ter
  • NP_001008213.1:p.Glu399Ter
  • NP_001008214.1:p.Glu399Ter
  • NP_068815.2:p.Glu399Ter
  • NC_000010.10:g.13167992G>T
Protein change:
E399*
Molecular consequence:
  • NM_001008211.1:c.1195G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001008212.2:c.1195G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001008213.1:c.1195G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_021980.4:c.1195G>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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002949886Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Mar 18, 2022) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

A novel OPTN variant causing PSP-CBS-like phenotype in familial amyotrophic lateral sclerosis.

Stezin A, Chaithra SP, Holla VV, Kamble N, Yadav R, Pal PK.

Parkinsonism Relat Disord. 2019 Dec;69:147-149. doi: 10.1016/j.parkreldis.2019.11.003. Epub 2019 Nov 9. No abstract available.

PubMed [citation]
PMID:
31759189

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
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002949886.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

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: 31759189). It has also been observed to segregate with disease in related individuals. This variant has been reported in individual(s) with autosomal dominant amyotrophic lateral sclerosis (Invitae); however, the role of the variant in this condition is currently unclear. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu399*) 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).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024