NM_130837.3(OPA1):c.1369G>A (p.Val457Met) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 14, 2023
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:: RCV003556273.2

Allele description [Variation Report for NM_130837.3(OPA1):c.1369G>A (p.Val457Met)]

NM_130837.3(OPA1):c.1369G>A (p.Val457Met)

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.1369G>A (p.Val457Met)

HGVS:

NC_000003.12:g.193643436G>A
NG_011605.1:g.55293G>A
NM_001354663.2:c.835G>A
NM_001354664.2:c.832G>A
NM_015560.3:c.1204G>A
NM_130831.3:c.1096G>A
NM_130832.3:c.1150G>A
NM_130833.3:c.1207G>A
NM_130834.3:c.1258G>A
NM_130835.3:c.1261G>A
NM_130836.3:c.1315G>A
NM_130837.3:c.1369G>AMANE SELECT
NP_001341592.1:p.Val279Met
NP_001341593.1:p.Val278Met
NP_056375.2:p.Val402Met
NP_056375.2:p.Val402Met
NP_570844.1:p.Val366Met
NP_570845.1:p.Val384Met
NP_570846.1:p.Val403Met
NP_570847.2:p.Val420Met
NP_570848.1:p.Val421Met
NP_570849.2:p.Val439Met
NP_570850.2:p.Val457Met
LRG_337t1:c.1204G>A
LRG_337:g.55293G>A
LRG_337p1:p.Val402Met
NC_000003.11:g.193361225G>A
NM_015560.2:c.1204G>A

Protein change:

V278M; VAL402MET

Links:

OMIM: 605290.0021; dbSNP: rs879255594

NCBI 1000 Genomes Browser:

rs879255594

Molecular consequence:

NM_001354663.2:c.835G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354664.2:c.832G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_015560.3:c.1204G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130831.3:c.1096G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130832.3:c.1150G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130833.3:c.1207G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130834.3:c.1258G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130835.3:c.1261G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130836.3:c.1315G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130837.3:c.1369G>A - 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
SCV004292250	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 14, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25012220, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004292250

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 14, 2023)

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

Early-onset Behr syndrome due to compound heterozygous mutations in OPA1.

Bonneau D, Colin E, Oca F, Ferré M, Chevrollier A, Guéguen N, Desquiret-Dumas V, N'Guyen S, Barth M, Zanlonghi X, Rio M, Desguerre I, Barnerias C, Momtchilova M, Rodriguez D, Slama A, Lenaers G, Procaccio V, Amati-Bonneau P, Reynier P.

Brain. 2014 Oct;137(Pt 10):e301. doi: 10.1093/brain/awu184. Epub 2014 Jul 10. No abstract available.

PubMed [citation]

PMID:: 25012220

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, SCV004292250.1

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

Description

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 not expected to disrupt OPA1 protein function. 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 225122). This variant is also known as c.1369G>A. This missense change has been observed in individual(s) with OPA1-related conditions (PMID: 25012220). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 402 of the OPA1 protein (p.Val402Met).

#	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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