NM_000088.4(COL1A1):c.1414C>T (p.Arg472Ter) AND Osteogenesis imperfecta type I

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 13, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000803118.8

Allele description [Variation Report for NM_000088.4(COL1A1):c.1414C>T (p.Arg472Ter)]

NM_000088.4(COL1A1):c.1414C>T (p.Arg472Ter)

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.1414C>T (p.Arg472Ter)

HGVS:

NC_000017.11:g.50194768G>A
NG_007400.1:g.11872C>T
NM_000088.4:c.1414C>TMANE SELECT
NP_000079.2:p.Arg472Ter
NP_000079.2:p.Arg472Ter
LRG_1t1:c.1414C>T
LRG_1:g.11872C>T
LRG_1p1:p.Arg472Ter
NC_000017.10:g.48272129G>A
NM_000088.3:c.1414C>T

Protein change:

R472*

Links:

dbSNP: rs72648343

NCBI 1000 Genomes Browser:

rs72648343

Molecular consequence:

NM_000088.4:c.1414C>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
SCV000942979	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 13, 2024)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 7942841, 9295084, 9443882, 16786509, 18311573, 22753364, 28492532
SCV004098667	Division of Genomic Medicine, Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 20, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000942979

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 13, 2024)

germline

clinical testing

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

SCV004098667

Division of Genomic Medicine, Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 20, 2023)

germline

clinical testing

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

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
Japanese	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

Ehlers-Danlos syndrome type VIIA and VIIB result from splice-junction mutations or genomic deletions that involve exon 6 in the COL1A1 and COL1A2 genes of type I collagen.

Byers PH, Duvic M, Atkinson M, Robinow M, Smith LT, Krane SM, Greally MT, Ludman M, Matalon R, Pauker S, Quanbeck D, Schwarze U.

Am J Med Genet. 1997 Oct 3;72(1):94-105.

PubMed [citation]

PMID:: 9295084

See all PubMed Citations (8)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000942979.6

#	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.Arg472*) 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with osteogenesis imperfecta type 1 (PMID: 16786509, 18311573, 22753364). ClinVar contains an entry for this variant (Variation ID: 449400). 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

From Division of Genomic Medicine, Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University, SCV004098667.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Japanese	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	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Oct 26, 2024

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