NM_130837.3(OPA1):c.1408A>G (p.Lys470Glu) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 28, 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:: RCV002035226.3

Allele description

NM_130837.3(OPA1):c.1408A>G (p.Lys470Glu)

Gene:

OPA1:OPA1 mitochondrial dynamin like GTPase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3q29

Genomic location:

Preferred name:

NM_130837.3(OPA1):c.1408A>G (p.Lys470Glu)

HGVS:

NC_000003.12:g.193643558A>G
NG_011605.1:g.55415A>G
NM_001354663.2:c.874A>G
NM_001354664.2:c.871A>G
NM_015560.3:c.1243A>G
NM_130831.3:c.1135A>G
NM_130832.3:c.1189A>G
NM_130833.3:c.1246A>G
NM_130834.3:c.1297A>G
NM_130835.3:c.1300A>G
NM_130836.3:c.1354A>G
NM_130837.3:c.1408A>GMANE SELECT
NP_001341592.1:p.Lys292Glu
NP_001341593.1:p.Lys291Glu
NP_056375.2:p.Lys415Glu
NP_570844.1:p.Lys379Glu
NP_570845.1:p.Lys397Glu
NP_570846.1:p.Lys416Glu
NP_570847.2:p.Lys433Glu
NP_570848.1:p.Lys434Glu
NP_570849.2:p.Lys452Glu
NP_570850.2:p.Lys470Glu
LRG_337:g.55415A>G
NC_000003.11:g.193361347A>G

Protein change:

K291E

Links:

dbSNP: rs2109044398

NCBI 1000 Genomes Browser:

rs2109044398

Molecular consequence:

NM_001354663.2:c.874A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354664.2:c.871A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_015560.3:c.1243A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_130831.3:c.1135A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_130832.3:c.1189A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_130833.3:c.1246A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_130834.3:c.1297A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_130835.3:c.1300A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_130836.3:c.1354A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_130837.3:c.1408A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002227897	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 28, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 27265430, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002227897

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 28, 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

Exome sequencing identified a novel de novo OPA1 mutation in a consanguineous family presenting with optic atrophy.

Cohen L, Tzur S, Goldenberg-Cohen N, Bormans C, Behar DM, Reinstein E.

Genet Res (Camb). 2016 Jun 6;98:e10. doi: 10.1017/S0016672316000070.

PubMed [citation]

PMID:: 27265430
PMCID:: PMC6865152

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 Invitae, SCV002227897.3

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

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt OPA1 protein function. This variant is also known as c.1189A>G (p.Lys397Glu). This missense change has been observed in individual(s) with autosomal dominant optic atrophy (PMID: 27265430). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with glutamic acid at codon 415 of the OPA1 protein (p.Lys415Glu). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamic acid.

#	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: Feb 14, 2024

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