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NM_002317.7(LOX):c.1021A>C (p.Thr341Pro) AND multiple conditions

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jan 5, 2021
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:
RCV001530398.1

Allele description

NM_002317.7(LOX):c.1021A>C (p.Thr341Pro)

Genes:
LOX:lysyl oxidase [Gene - OMIM - HGNC]
SRFBP1:serum response factor binding protein 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
5q23.1
Genomic location:
Preferred name:
NM_002317.7(LOX):c.1021A>C (p.Thr341Pro)
HGVS:
  • NC_000005.10:g.122074027T>G
  • NG_008722.1:g.9334A>C
  • NM_001178102.2:c.331A>C
  • NM_001317073.1:c.130A>C
  • NM_002317.7:c.1021A>CMANE SELECT
  • NP_001171573.1:p.Thr111Pro
  • NP_001304002.1:p.Thr44Pro
  • NP_002308.2:p.Thr341Pro
  • NC_000005.9:g.121409722T>G
  • NM_002317.5:c.1021A>C
Protein change:
T111P
Links:
dbSNP: rs1436353084
NCBI 1000 Genomes Browser:
rs1436353084
Molecular consequence:
  • NM_001178102.2:c.331A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001317073.1:c.130A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002317.7:c.1021A>C - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
loss_of_function_variant [Sequence Ontology: SO:0002054]
Observations:
1

Condition(s)

Name:
Cutis laxa
Identifiers:
MONDO: MONDO:0016175; MedGen: C0010495; Human Phenotype Ontology: HP:0000973
Name:
Generalized arterial tortuosity
Identifiers:
MedGen: C1836651; Human Phenotype Ontology: HP:0004955

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001468319Center for Medical Genetics Ghent, University of Ghent
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Jan 5, 2021) 		inheritedclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedinheritedyes1not providednot providednot providednot providedclinical 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 Center for Medical Genetics Ghent, University of Ghent, SCV001468319.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
11not providednot providedclinical testing PubMed (1)

Description

Several lines of evidence support the pathogenicity of the LOX variants in the patients’ phenotype. Firstly, the mutation is located in the catalytic domain, absent in control databases and predicted deleterious by all in silico prediction algorithms including Polyphen2, SIFT, Provean and Mutation Taster. Secondly, Lysyl oxidase directly interacts with Fibulin-4 (EFEMP2), the protein deficient in ARCL1B, with similar clinical effects on the vasculature, skin (cutis laxa), skeleton and respiratory system (including diaphragmatic abnormalities). Thirdly, several LOX knockout mouse models (Lox-/-) have been generated that presented with a very similar clinical phenotype to that seen in our patients. Fourthly, the ultrastructural findings can be interpreted as showing a significant fault in elastogenesis; the microfibrillar scaffolding of the elastic fibre is forming but the actual assembly of elastin in its interstices is minimal, all of which is consistent with a lysyl oxidase anomaly 6.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1inheritedyesnot providednot providednot provided1not providednot providednot provided

Last Updated: Dec 24, 2023