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NM_000089.4(COL1A2):c.1268G>A (p.Arg423His) AND Cardiovascular phenotype

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Oct 26, 2020
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:
RCV002376891.3

Allele description [Variation Report for NM_000089.4(COL1A2):c.1268G>A (p.Arg423His)]

NM_000089.4(COL1A2):c.1268G>A (p.Arg423His)

Gene:
COL1A2:collagen type I alpha 2 chain [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7q21.3
Genomic location:
Preferred name:
NM_000089.4(COL1A2):c.1268G>A (p.Arg423His)
HGVS:
  • NC_000007.14:g.94411072G>A
  • NG_007405.1:g.21512G>A
  • NM_000089.4:c.1268G>AMANE SELECT
  • NP_000080.2:p.Arg423His
  • NP_000080.2:p.Arg423His
  • LRG_2t1:c.1268G>A
  • LRG_2:g.21512G>A
  • LRG_2p1:p.Arg423His
  • NC_000007.13:g.94040384G>A
  • NM_000089.3:c.1268G>A
Protein change:
R423H
Links:
dbSNP: rs764780528
NCBI 1000 Genomes Browser:
rs764780528
Molecular consequence:
  • NM_000089.4:c.1268G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002685130Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Oct 26, 2020) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Genetic epidemiology, prevalence, and genotype-phenotype correlations in the Swedish population with osteogenesis imperfecta.

Lindahl K, Åström E, Rubin CJ, Grigelioniene G, Malmgren B, Ljunggren Ö, Kindmark A.

Eur J Hum Genet. 2015 Aug;23(8):1042-50. doi: 10.1038/ejhg.2015.81. Epub 2015 May 6. Erratum in: Eur J Hum Genet. 2015 Aug;23(8):1112. doi: 10.1038/ejhg.2015.129.

PubMed [citation]
PMID:
25944380
PMCID:
PMC4795106

Tooth agenesis in osteogenesis imperfecta related to mutations in the collagen type I genes.

Malmgren B, Andersson K, Lindahl K, Kindmark A, Grigelioniene G, Zachariadis V, Dahllöf G, Åström E.

Oral Dis. 2017 Jan;23(1):42-49. doi: 10.1111/odi.12568. Epub 2016 Sep 13.

PubMed [citation]
PMID:
27510842
See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV002685130.2

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

Description

The p.R423H variant (also known as c.1268G>A), located in coding exon 23 of the COL1A2 gene, results from a G to A substitution at nucleotide position 1268. The arginine at codon 423 is replaced by histidine, an amino acid with highly similar properties. This variant has been reported in osteogenesis imperfecta cohorts, including type III and type IV cases; however, in one case, this variant was inherited from an unaffected mother, and a de novo COL1A2 splicing mutation was also detected in the proband (Lindahl K et al. Eur J Hum Genet, 2015 Aug;23:1042-50; Li L et al. Hum Mutat, 2019 05;40:588-600). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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

Last Updated: Oct 20, 2024