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NM_005138.3(SCO2):c.358C>T (p.Arg120Trp) AND not provided

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Jul 13, 2023
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV003097786.3

Allele description [Variation Report for NM_005138.3(SCO2):c.358C>T (p.Arg120Trp)]

NM_005138.3(SCO2):c.358C>T (p.Arg120Trp)

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.358C>T (p.Arg120Trp)
HGVS:
  • NC_000022.11:g.50524054G>A
  • NG_011860.1:g.11032C>T
  • NG_016235.1:g.7386C>T
  • NG_021419.1:g.20839G>A
  • NM_001169109.2:c.358C>T
  • NM_001169110.1:c.358C>T
  • NM_001169111.2:c.358C>T
  • NM_001185011.2:c.*679G>A
  • NM_005138.3:c.358C>TMANE SELECT
  • NM_152299.4:c.*679G>AMANE SELECT
  • NP_001162580.1:p.Arg120Trp
  • NP_001162581.1:p.Arg120Trp
  • NP_001162582.1:p.Arg120Trp
  • NP_005129.2:p.Arg120Trp
  • LRG_727:g.11032C>T
  • NC_000022.10:g.50962483G>A
  • NM_005138.2:c.358C>T
Protein change:
R120W
Molecular consequence:
  • NM_001185011.2:c.*679G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_152299.4:c.*679G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001169109.2:c.358C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001169110.1:c.358C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001169111.2:c.358C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_005138.3:c.358C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002931359Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Oct 16, 2022) 		germlineclinical testing

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

SCV004014190GeneDx
criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)		Uncertain significance
(Jul 13, 2023) 		germlineclinical testing

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

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, SCV002931359.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 120 of the SCO2 protein (p.Arg120Trp). This variant is present in population databases (rs375954523, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with SCO2-related conditions. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SCO2 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.

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

From GeneDx, SCV004014190.1

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

Description

Observed with another variant in a patient with CMT type 4; however, it is unclear whether the variants are on the same allele (in cis) or on opposite alleles (in trans) (Chen et al., 2023); Observed in a patient with high myopia; however, additional clinical information was not provided (Jiang et al., 2015); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 31472110, 29386878, 37066920, 34222226, 25525168)

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

Last Updated: Sep 29, 2024