NM_130837.3(OPA1):c.1345A>G (p.Met449Val) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 26, 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:: RCV002800028.2

Allele description [Variation Report for NM_130837.3(OPA1):c.1345A>G (p.Met449Val)]

NM_130837.3(OPA1):c.1345A>G (p.Met449Val)

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.1345A>G (p.Met449Val)

HGVS:

NC_000003.12:g.193643412A>G
NG_011605.1:g.55269A>G
NM_001354663.2:c.811A>G
NM_001354664.2:c.808A>G
NM_015560.3:c.1180A>G
NM_130831.3:c.1072A>G
NM_130832.3:c.1126A>G
NM_130833.3:c.1183A>G
NM_130834.3:c.1234A>G
NM_130835.3:c.1237A>G
NM_130836.3:c.1291A>G
NM_130837.3:c.1345A>GMANE SELECT
NP_001341592.1:p.Met271Val
NP_001341593.1:p.Met270Val
NP_056375.2:p.Met394Val
NP_056375.2:p.Met394Val
NP_570844.1:p.Met358Val
NP_570845.1:p.Met376Val
NP_570846.1:p.Met395Val
NP_570847.2:p.Met412Val
NP_570848.1:p.Met413Val
NP_570849.2:p.Met431Val
NP_570850.2:p.Met449Val
NP_570850.2:p.Met449Val
LRG_337t1:c.1180A>G
LRG_337t2:c.1345A>G
LRG_337:g.55269A>G
LRG_337p1:p.Met394Val
LRG_337p2:p.Met449Val
NC_000003.11:g.193361201A>G
NM_015560.2:c.1180A>G
NM_130837.2:c.1345A>G

Protein change:

M270V

Molecular consequence:

NM_001354663.2:c.811A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354664.2:c.808A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_015560.3:c.1180A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_130831.3:c.1072A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_130832.3:c.1126A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_130833.3:c.1183A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_130834.3:c.1234A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_130835.3:c.1237A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_130836.3:c.1291A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_130837.3:c.1345A>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
SCV003028631	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 26, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 34242285, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003028631

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 26, 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

Mutation spectrum of the OPA1 gene in a large cohort of patients with suspected dominant optic atrophy: Identification and classification of 48 novel variants.

Weisschuh N, Schimpf-Linzenbold S, Mazzola P, Kieninger S, Xiao T, Kellner U, Neuhann T, Kelbsch C, Tonagel F, Wilhelm H, Kohl S, Wissinger B.

PLoS One. 2021;16(7):e0253987. doi: 10.1371/journal.pone.0253987.

PubMed [citation]

PMID:: 34242285
PMCID:: PMC8270428

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, SCV003028631.2

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

Description

This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 394 of the OPA1 protein (p.Met394Val). This variant is present in population databases (rs773887827, gnomAD 0.004%). This missense change has been observed in individual(s) with OPA1-related conditions (PMID: 34242285). ClinVar contains an entry for this variant (Variation ID: 1983543). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.

#	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: Mar 5, 2024

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