U.S. flag

An official website of the United States government

NM_001079866.2(BCS1L):c.325C>T (p.Arg109Trp) AND not provided

Germline classification:
Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:
Nov 7, 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:
RCV000199842.6

Allele description [Variation Report for NM_001079866.2(BCS1L):c.325C>T (p.Arg109Trp)]

NM_001079866.2(BCS1L):c.325C>T (p.Arg109Trp)

Gene:
BCS1L:BCS1 homolog, ubiquinol-cytochrome c reductase complex chaperone [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q35
Genomic location:
Preferred name:
NM_001079866.2(BCS1L):c.325C>T (p.Arg109Trp)
Other names:
p.R109W:CGG>TGG
HGVS:
  • NC_000002.12:g.218661410C>T
  • NG_008018.1:g.6755C>T
  • NG_033099.1:g.3131G>A
  • NM_001079866.2:c.325C>TMANE SELECT
  • NM_001257342.2:c.325C>T
  • NM_001257343.2:c.325C>T
  • NM_001257344.2:c.325C>T
  • NM_001318836.2:c.-36C>T
  • NM_001320717.2:c.325C>T
  • NM_001371443.1:c.325C>T
  • NM_001371444.1:c.325C>T
  • NM_001371446.1:c.325C>T
  • NM_001371447.1:c.325C>T
  • NM_001371448.1:c.325C>T
  • NM_001371449.1:c.325C>T
  • NM_001371450.1:c.325C>T
  • NM_001371451.1:c.-36C>T
  • NM_001371452.1:c.-41-349C>T
  • NM_001371453.1:c.-152C>T
  • NM_001371454.1:c.-152C>T
  • NM_001371455.1:c.-152C>T
  • NM_001371456.1:c.-152C>T
  • NM_001374085.1:c.325C>T
  • NM_001374086.1:c.-152C>T
  • NM_004328.5:c.325C>T
  • NP_001073335.1:p.Arg109Trp
  • NP_001244271.1:p.Arg109Trp
  • NP_001244272.1:p.Arg109Trp
  • NP_001244273.1:p.Arg109Trp
  • NP_001307646.1:p.Arg109Trp
  • NP_001358372.1:p.Arg109Trp
  • NP_001358373.1:p.Arg109Trp
  • NP_001358375.1:p.Arg109Trp
  • NP_001358376.1:p.Arg109Trp
  • NP_001358377.1:p.Arg109Trp
  • NP_001358378.1:p.Arg109Trp
  • NP_001358379.1:p.Arg109Trp
  • NP_001361014.1:p.Arg109Trp
  • NP_004319.1:p.Arg109Trp
  • NP_004319.1:p.Arg109Trp
  • LRG_539t1:c.325C>T
  • LRG_539:g.6755C>T
  • LRG_539p1:p.Arg109Trp
  • NC_000002.11:g.219526133C>T
  • NM_004328.4:c.325C>T
  • NR_163955.1:n.1337C>T
Protein change:
R109W
Links:
dbSNP: rs141257714
NCBI 1000 Genomes Browser:
rs141257714
Molecular consequence:
  • NM_001318836.2:c.-36C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001371451.1:c.-36C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001371453.1:c.-152C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001371454.1:c.-152C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001371455.1:c.-152C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001371456.1:c.-152C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001374086.1:c.-152C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001371452.1:c.-41-349C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001079866.2:c.325C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001257342.2:c.325C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001257343.2:c.325C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001257344.2:c.325C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001320717.2:c.325C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371443.1:c.325C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371444.1:c.325C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371446.1:c.325C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371447.1:c.325C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371448.1:c.325C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371449.1:c.325C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371450.1:c.325C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374085.1:c.325C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004328.5:c.325C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_163955.1:n.1337C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000251200GeneDx
criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)
Likely pathogenic
(Oct 4, 2023)
germlineclinical testing

Citation Link,

SCV003299179Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Nov 7, 2023)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

Expanding the phenotypic spectrum of BCS1L-related mitochondrial disease.

Hikmat O, Isohanni P, Keshavan N, Ferla MP, Fassone E, Abbott MA, Bellusci M, Darin N, Dimmock D, Ghezzi D, Houlden H, Invernizzi F, Kamarus Jaman NB, Kurian MA, Morava E, Naess K, Ortigoza-Escobar JD, Parikh S, Pennisi A, Barcia G, Tylleskär KB, Brackman D, et al.

Ann Clin Transl Neurol. 2021 Nov;8(11):2155-2165. doi: 10.1002/acn3.51470. Epub 2021 Oct 18.

PubMed [citation]
PMID:
34662929
PMCID:
PMC8607453

Molecular genetic investigations identify new clinical phenotypes associated with BCS1L-related mitochondrial disease.

Oláhová M, Ceccatelli Berti C, Collier JJ, Alston CL, Jameson E, Jones SA, Edwards N, He L, Chinnery PF, Horvath R, Goffrini P, Taylor RW, Sayer JA.

Hum Mol Genet. 2019 Nov 15;28(22):3766-3776. doi: 10.1093/hmg/ddz202.

PubMed [citation]
PMID:
31435670
PMCID:
PMC6935384
See all PubMed Citations (3)

Details of each submission

From GeneDx, SCV000251200.13

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

Description

Functional studies found R109W was unable to rescue oxidation phosphorylation phenotype of BSCIL deficient yeast cells (Olahova et al., 2019); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 34662929, 31435670)

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

From Invitae, SCV003299179.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 109 of the BCS1L protein (p.Arg109Trp). This variant is present in population databases (rs141257714, gnomAD 0.03%). This missense change has been observed in individuals with BCS1L-related conditions (PMID: 31435670, 34662929). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 214166). 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) performed at Invitae indicates that this missense variant is expected to disrupt BCS1L protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects BCS1L function (PMID: 31435670). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Jun 17, 2024