U.S. flag

An official website of the United States government

NM_000088.4(COL1A1):c.333+1G>C AND Osteogenesis imperfecta type I

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 6, 2022
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:
RCV002847588.2

Allele description [Variation Report for NM_000088.4(COL1A1):c.333+1G>C]

NM_000088.4(COL1A1):c.333+1G>C

Gene:
COL1A1:collagen type I alpha 1 chain [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q21.33
Genomic location:
Preferred name:
NM_000088.4(COL1A1):c.333+1G>C
HGVS:
  • NC_000017.11:g.50199555C>G
  • NG_007400.1:g.7085G>C
  • NM_000088.4:c.333+1G>CMANE SELECT
  • LRG_1:g.7085G>C
  • NC_000017.10:g.48276916C>G
Molecular consequence:
  • NM_000088.4:c.333+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Osteogenesis imperfecta type I (OI1)
Synonyms:
OI, TYPE I; Osteogenesis imperfecta type 1; OI type 1; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0008146; MedGen: C0023931; Orphanet: 666; OMIM: 166200

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003227765Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Aug 6, 2022) 		germlineclinical testing

PubMed (8)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933

Osteogenesis imperfecta type I: molecular heterogeneity for COL1A1 null alleles of type I collagen.

Willing MC, Deschenes SP, Scott DA, Byers PH, Slayton RL, Pitts SH, Arikat H, Roberts EJ.

Am J Hum Genet. 1994 Oct;55(4):638-47.

PubMed [citation]
PMID:
7942841
PMCID:
PMC1918287
See all PubMed Citations (8)

Details of each submission

From Invitae, SCV003227765.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (8)

Description

This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 3 of the COL1A1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in COL1A1 are known to be pathogenic (PMID: 7942841, 9295084, 9443882). Disruption of this splice site has been observed in individuals with osteogenesis imperfecta (PMID: 15024745, 25963598, 30715774). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site.

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

Last Updated: Feb 20, 2024