NM_005138.3(SCO2):c.303G>C (p.Gln101His) AND Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 28, 2019
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:: RCV004789546.1

Allele description [Variation Report for NM_005138.3(SCO2):c.303G>C (p.Gln101His)]

NM_005138.3(SCO2):c.303G>C (p.Gln101His)

Genes:

NCAPH2:non-SMC condensin II complex subunit H2 [Gene - OMIM - HGNC]
SCO2:synthesis of cytochrome C oxidase 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

22q13.33

Genomic location:

Preferred name:

NM_005138.3(SCO2):c.303G>C (p.Gln101His)

HGVS:

NC_000022.11:g.50524109C>G
NG_011860.1:g.10977G>C
NG_016235.1:g.7331G>C
NG_021419.1:g.20894C>G
NM_001169109.2:c.303G>C
NM_001169110.1:c.303G>C
NM_001169111.2:c.303G>C
NM_001185011.2:c.*734C>G
NM_005138.3:c.303G>CMANE SELECT
NM_152299.4:c.*734C>GMANE SELECT
NP_001162580.1:p.Gln101His
NP_001162581.1:p.Gln101His
NP_001162582.1:p.Gln101His
NP_005129.2:p.Gln101His
LRG_727:g.10977G>C
NC_000022.10:g.50962538C>G
NM_005138.2:c.303G>C
p.Gln101His

Protein change:

Q101H

Links:

dbSNP: rs141551295

NCBI 1000 Genomes Browser:

rs141551295

Molecular consequence:

NM_001185011.2:c.*734C>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_152299.4:c.*734C>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001169109.2:c.303G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001169110.1:c.303G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001169111.2:c.303G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_005138.3:c.303G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1 (MC4DN2)
Synonyms:: CYTOCHROME c OXIDASE DEFICIENCY, FATAL INFANTILE, WITH CARDIOENCEPHALOMYOPATHY; Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency; MITOCHONDRIAL COMPLEX IV DEFICIENCY, NUCLEAR TYPE 2
Identifiers:: MONDO: MONDO:0011451; MedGen: C5399977; Orphanet: 1561; OMIM: 604377

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005398077	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Aug 28, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005398077

Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Aug 28, 2019)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV005398077.1

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

Description

A heterozygous missense variant was identified, NM_005138.2(SCO2):c.303G>C in exon 2 of 2 of the SCO2 gene. This substitution is predicted to create a minor amino acid change from glutamine to histidine at position 101 of the protein, NP_005129.2(SCO2):p.(Gln101His). The glutamine at this position has moderate conservation (100 vertebrates, UCSC), and is located within the thioredoxin functional domain. In silico software predicts this variant to be disease causing. The variant is present in the gnomAD population database at a frequency of 0.0071% (20 heterozygotes, 0 homozygotes). The variant has not been previously reported in a clinical case. Analysis of parental samples indicates that this variant is paternally inherited. Based on information available at the time of curation, this variant has been classified as a VARIANT of UNCERTAIN SIGNIFICANCE (VUS).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 24, 2024

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