NM_004208.4(AIFM1):c.893G>A (p.Arg298Gln) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 31, 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:: RCV000811082.8

Allele description [Variation Report for NM_004208.4(AIFM1):c.893G>A (p.Arg298Gln)]

NM_004208.4(AIFM1):c.893G>A (p.Arg298Gln)

Genes:

RAB33A:RAB33A, member RAS oncogene family [Gene - OMIM - HGNC]
AIFM1:apoptosis inducing factor mitochondria associated 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq26.1

Genomic location:

Preferred name:

NM_004208.4(AIFM1):c.893G>A (p.Arg298Gln)

HGVS:

NC_000023.11:g.130138667C>T
NG_013217.1:g.32167G>A
NM_001130847.4:c.893G>A
NM_004208.4:c.893G>AMANE SELECT
NM_145812.3:c.881G>A
NP_001124319.1:p.Arg298Gln
NP_004199.1:p.Arg298Gln
NP_665811.1:p.Arg294Gln
NC_000023.10:g.129272642C>T
NM_004208.3:c.893G>A
NR_132647.2:n.935G>A

Protein change:

R294Q

Links:

dbSNP: rs766786579

NCBI 1000 Genomes Browser:

rs766786579

Molecular consequence:

NM_001130847.4:c.893G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_004208.4:c.893G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_145812.3:c.881G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_132647.2:n.935G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Charcot-Marie-Tooth Neuropathy X
Identifiers:: MedGen: CN118851

Name:: Combined oxidative phosphorylation deficiency
Identifiers:: MONDO: MONDO:0000732; MedGen: C4540031; OMIM: PS609060

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Mus musculus, clone IMAGE:1478834, mRNA
Mus musculus, clone IMAGE:1478834, mRNA
gi|22713526|gb|BC037370.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000951329	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 31, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29625556, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000951329

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 31, 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

Targeted next generation sequencing with an extended gene panel does not impact variant detection in mitochondrial diseases.

Plutino M, Chaussenot A, Rouzier C, Ait-El-Mkadem S, Fragaki K, Paquis-Flucklinger V, Bannwarth S.

BMC Med Genet. 2018 Apr 7;19(1):57. doi: 10.1186/s12881-018-0568-y.

PubMed [citation]

PMID:: 29625556
PMCID:: PMC5889585

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, SCV000951329.5

#	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 arginine with glutamine at codon 298 of the AIFM1 protein (p.Arg298Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs766786579, ExAC 0.03%). This missense change has been observed in individual(s) with chronic progressive external ophthalmoplegia and dysphagia (PMID: 29625556). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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: Sep 29, 2024

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