NM_005138.3(SCO2):c.227_230del (p.Leu76fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 22, 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:: RCV003699027.2

Allele description [Variation Report for NM_005138.3(SCO2):c.227_230del (p.Leu76fs)]

NM_005138.3(SCO2):c.227_230del (p.Leu76fs)

Genes:

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

Variant type:

Microsatellite

Cytogenetic location:

22q13.33

Genomic location:

Preferred name:

NM_005138.3(SCO2):c.227_230del (p.Leu76fs)

HGVS:

NC_000022.11:g.50524183CCAG[1]
NG_011860.1:g.10897TGGC[1]
NG_016235.1:g.7251TGGC[1]
NG_021419.1:g.20968CCAG[1]
NM_001169109.2:c.227_230del
NM_001169110.1:c.227_230del
NM_001169111.2:c.227_230del
NM_001185011.2:c.*808CCAG[1]
NM_005138.3:c.227_230delMANE SELECT
NM_152299.4:c.*808CCAG[1]MANE SELECT
NP_001162580.1:p.Leu76fs
NP_001162581.1:p.Leu76fs
NP_001162582.1:p.Leu76fs
NP_005129.2:p.Leu76fs
LRG_727:g.10897TGGC[1]
NC_000022.10:g.50962611_50962614del
NC_000022.10:g.50962612CCAG[1]
NM_005138.2:c.227_230del

Protein change:

L76fs

Molecular consequence:

NM_001185011.2:c.*808CCAG[1] - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_152299.4:c.*808CCAG[1] - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001169109.2:c.227_230del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001169110.1:c.227_230del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001169111.2:c.227_230del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_005138.3:c.227_230del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004462619	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 22, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 19353847, 29193756, 32600061, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004462619

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 22, 2023)

germline

clinical testing

PubMed (4)
[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

A novel homozygous SCO2 mutation, p.G193S, causing fatal infantile cardioencephalomyopathy.

Mobley BC, Enns GM, Wong LJ, Vogel H.

Clin Neuropathol. 2009 Mar-Apr;28(2):143-9.

PubMed [citation]

PMID:: 19353847

Investigating the cardiac pathology of SCO2-mediated hypertrophic cardiomyopathy using patients induced pluripotent stem cell-derived cardiomyocytes.

Hallas T, Eisen B, Shemer Y, Ben Jehuda R, Mekies LN, Naor S, Schick R, Eliyahu S, Reiter I, Vlodavsky E, Katz YS, Õunap K, Lorber A, Rodenburg R, Mandel H, Gherghiceanu M, Binah O.

J Cell Mol Med. 2018 Feb;22(2):913-925. doi: 10.1111/jcmm.13392. Epub 2017 Nov 28.

PubMed [citation]

PMID:: 29193756
PMCID:: PMC5783844

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004462619.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Leu76Profs*2) in the SCO2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 191 amino acid(s) of the SCO2 protein. This variant is present in population databases (rs780824645, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with SCO2-related conditions. This variant disrupts a region of the SCO2 protein in which other variant(s) (p.Gln182*) have been determined to be pathogenic (PMID: 19353847, 29193756, 32600061). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#	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

ClinVar

Relating variation to medicine