NM_130837.3(OPA1):c.1126A>G (p.Met376Val) AND not provided

Clinical significance:Likely pathogenic (Last evaluated: Jul 17, 2014)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000198713.1

Allele description [Variation Report for NM_130837.3(OPA1):c.1126A>G (p.Met376Val)]

NM_130837.3(OPA1):c.1126A>G (p.Met376Val)

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.1126A>G (p.Met376Val)
HGVS:
  • NC_000003.12:g.193638042A>G
  • NG_011605.1:g.49899A>G
  • NM_001354663.2:c.592A>G
  • NM_001354664.2:c.589A>G
  • NM_015560.2:c.961A>G
  • NM_015560.3:c.961A>G
  • NM_130831.3:c.853A>G
  • NM_130832.3:c.907A>G
  • NM_130833.3:c.964A>G
  • NM_130834.3:c.1015A>G
  • NM_130835.3:c.1018A>G
  • NM_130836.3:c.1072A>G
  • NM_130837.3:c.1126A>GMANE SELECT
  • NP_001341592.1:p.Met198Val
  • NP_001341593.1:p.Met197Val
  • NP_056375.2:p.Met321Val
  • NP_056375.2:p.Met321Val
  • NP_570844.1:p.Met285Val
  • NP_570845.1:p.Met303Val
  • NP_570846.1:p.Met322Val
  • NP_570847.2:p.Met339Val
  • NP_570848.1:p.Met340Val
  • NP_570849.2:p.Met358Val
  • NP_570850.2:p.Met376Val
  • LRG_337t1:c.961A>G
  • LRG_337:g.49899A>G
  • LRG_337p1:p.Met321Val
  • NC_000003.11:g.193355831A>G
  • p.M321V
Protein change:
M197V
Links:
dbSNP: rs863224132
NCBI 1000 Genomes Browser:
rs863224132
Molecular consequence:
  • NM_001354663.2:c.592A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354664.2:c.589A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_015560.2:c.961A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_015560.3:c.961A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_130831.3:c.853A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_130832.3:c.907A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_130833.3:c.964A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_130834.3:c.1015A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_130835.3:c.1018A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_130836.3:c.1072A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_130837.3:c.1126A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000251991GeneDxcriteria provided, single submitter
Likely pathogenic
(Jul 17, 2014)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000251991.10

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

p.Met321Val (ATG>GTG): c.961 A>G in exon 9 of the OPA1 gene (NM_015560.2). The M321V variant that is likely pathogenic was identified in the OPA1 gene. It has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The M321V variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The M321V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense mutations in nearby residues (I313K, T330S and L331P) have been reported in association with optic atrophy, supporting the functional importance of this region of the protein. Therefore, this variant is a strong candidate for a pathogenic mutation, however the possibility that it is a benign variant cannot be excluded. The variant is found in MITONUC-MITOP panel(s).

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

Last Updated: Oct 25, 2021

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