NM_000088.4(COL1A1):c.2089C>T (p.Arg697Ter) AND Osteogenesis imperfecta type I

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Dec 22, 2023
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:: RCV000358677.12

Allele description [Variation Report for NM_000088.4(COL1A1):c.2089C>T (p.Arg697Ter)]

NM_000088.4(COL1A1):c.2089C>T (p.Arg697Ter)

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.2089C>T (p.Arg697Ter)

HGVS:

NC_000017.11:g.50191826G>A
NG_007400.1:g.14814C>T
NM_000088.4:c.2089C>TMANE SELECT
NP_000079.2:p.Arg697Ter
NP_000079.2:p.Arg697Ter
LRG_1t1:c.2089C>T
LRG_1:g.14814C>T
LRG_1p1:p.Arg697Ter
NC_000017.10:g.48269187G>A
NM_000088.3:c.2089C>T

Protein change:

R697*

Links:

dbSNP: rs72651642

NCBI 1000 Genomes Browser:

rs72651642

Molecular consequence:

NM_000088.4:c.2089C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000574599	Department of Medical Sciences, Uppsala University See additional submitters Department of Dental Medicine, Karolinska Institutet	no assertion criteria provided	Pathogenic	maternal	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000627195	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 22, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 7942841, 9295084, 9443882, 8808594, 21667357, 28378289, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000574599

Department of Medical Sciences, Uppsala University

See additional submitters

no assertion criteria provided

Pathogenic

maternal

clinical testing

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

SCV000627195

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 22, 2023)

germline

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	maternal	yes	1	not provided	not provided	1	not provided	clinical 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

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 Department of Medical Sciences, Uppsala University, SCV000574599.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	maternal	yes	1	not provided	not provided		1	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000627195.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This sequence change creates a premature translational stop signal (p.Arg697*) in the COL1A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COL1A1 are known to be pathogenic (PMID: 7942841, 9295084, 9443882). This variant is present in population databases (rs72651642, gnomAD 0.007%). This premature translational stop signal has been observed in individuals with osteogenesis imperfecta (PMID: 8808594, 21667357, 28378289). ClinVar contains an entry for this variant (Variation ID: 287320). For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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