NM_001008212.2(OPTN):c.247C>T (p.Arg83Cys) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 23, 2021
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:: RCV001859779.4

Allele description [Variation Report for NM_001008212.2(OPTN):c.247C>T (p.Arg83Cys)]

NM_001008212.2(OPTN):c.247C>T (p.Arg83Cys)

Genes:

LOC108903148:10p13 OPTN distal Alu-mediated recombination region [Gene]
OPTN:optineurin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10p13

Genomic location:

Preferred name:

NM_001008212.2(OPTN):c.247C>T (p.Arg83Cys)

HGVS:

NC_000010.11:g.13110354C>T
NG_012876.1:g.15273C>T
NG_051826.1:g.1910C>T
NM_001008211.1:c.247C>T
NM_001008212.2:c.247C>TMANE SELECT
NM_001008213.1:c.247C>T
NM_021980.4:c.247C>T
NP_001008212.1:p.Arg83Cys
NP_001008213.1:p.Arg83Cys
NP_001008214.1:p.Arg83Cys
NP_068815.2:p.Arg83Cys
NC_000010.10:g.13152354C>T

Protein change:

R83C

Links:

dbSNP: rs756622651

NCBI 1000 Genomes Browser:

rs756622651

Molecular consequence:

NM_001008211.1:c.247C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001008212.2:c.247C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001008213.1:c.247C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_021980.4:c.247C>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV002160835	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 23, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 32893042, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002160835

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 23, 2021)

germline

clinical testing

PubMed (2)
[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

Four novel optineurin mutations in patients with sporadic amyotrophic lateral sclerosis in Mainland China.

Yang L, Cheng Y, Jia X, Liu X, Li X, Zhang K, Shen D, Liu M, Guan Y, Liu Q, Cui L, Li X.

Neurobiol Aging. 2021 Jan;97:149.e1-149.e8. doi: 10.1016/j.neurobiolaging.2020.08.002. Epub 2020 Aug 8.

PubMed [citation]

PMID:: 32893042

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002160835.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 299209). This missense change has been observed in individuals with autosomal dominant amyotrophic lateral sclerosis (PMID: 32893042; Invitae). This variant is present in population databases (rs756622651, ExAC 0.002%). This sequence change replaces arginine with cysteine at codon 83 of the OPTN protein (p.Arg83Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine.

#	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: Sep 29, 2024

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Relating variation to medicine