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NM_019095.6(CRLS1):c.515C>A (p.Ala172Asp) AND Combined oxidative phosphorylation deficiency 57

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 6, 2023
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV003152311.1

Allele description [Variation Report for NM_019095.6(CRLS1):c.515C>A (p.Ala172Asp)]

NM_019095.6(CRLS1):c.515C>A (p.Ala172Asp)

Gene:
CRLS1:cardiolipin synthase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
20p12.3
Genomic location:
Preferred name:
NM_019095.6(CRLS1):c.515C>A (p.Ala172Asp)
HGVS:
  • NC_000020.11:g.6015431C>A
  • NM_001127458.2:c.218C>A
  • NM_001323561.2:c.182C>A
  • NM_001323562.2:c.182C>A
  • NM_001323563.2:c.182C>A
  • NM_001323564.2:c.182C>A
  • NM_019095.6:c.515C>AMANE SELECT
  • NP_001120930.1:p.Ala73Asp
  • NP_001310490.1:p.Ala61Asp
  • NP_001310491.1:p.Ala61Asp
  • NP_001310492.1:p.Ala61Asp
  • NP_001310493.1:p.Ala61Asp
  • NP_061968.1:p.Ala172Asp
  • NC_000020.10:g.5996077C>A
  • NR_136617.2:n.639C>A
Protein change:
A172D; ALA172ASP
Links:
OMIM: 608188.0002
Molecular consequence:
  • NM_001127458.2:c.218C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001323561.2:c.182C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001323562.2:c.182C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001323563.2:c.182C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001323564.2:c.182C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_019095.6:c.515C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_136617.2:n.639C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Combined oxidative phosphorylation deficiency 57 (COXPD57)
Identifiers:
MONDO: MONDO:0859337; MedGen: C5774275; OMIM: 620167

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003840900OMIM
no assertion criteria provided
Pathogenic
(Jan 6, 2023) 		germlineliterature only

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Deleterious variants in CRLS1 lead to cardiolipin deficiency and cause an autosomal recessive multi-system mitochondrial disease.

Lee RG, Balasubramaniam S, Stentenbach M, Kralj T, McCubbin T, Padman B, Smith J, Riley LG, Priyadarshi A, Peng L, Nuske MR, Webster R, Peacock K, Roberts P, Stark Z, Lemire G, Ito YA; Care4Rare Canada Consortium., Boycott KM, Geraghty MT, van Klinken JB, Ferdinandusse S, et al.

Hum Mol Genet. 2022 Oct 28;31(21):3597-3612. doi: 10.1093/hmg/ddac040. Erratum in: Hum Mol Genet. 2023 Mar 20;32(7):1236. doi: 10.1093/hmg/ddac294.

PubMed [citation]
PMID:
35147173
PMCID:
PMC9616573

Details of each submission

From OMIM, SCV003840900.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In a Caucasian patient (subject 2, family 3) with combined oxidative phosphorylation deficiency-57 (COXPD57; 620167), Lee et al. (2022) identified compound heterozygous mutations in the CRLS1 gene: a c.515C-A transversion (c.515C-A, NM_019095.6), resulting in an ala172-to-asp (A172D) substitution, and a c.649C-T transition, resulting in a leu217-to-phe (L217F; 608188.0003) substitution. The mutations were identified by whole-exome sequencing and segregated with the disorder in the family. A172D was not present in the gnomAD database (v2.1.1) and L217F was present at an allele frequency of 0.0016%. Lipidomic analysis demonstrated a trend towards decreased cardiolipin in fibroblasts from the patient compared to controls and an elevation of the CRLS1 substrate phosphatidylglycerol.

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

Last Updated: Jun 3, 2023