NM_000088.4(COL1A1):c.387del (p.Gly130fs) AND Osteogenesis imperfecta type I

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Feb 10, 2022
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:: RCV000540153.8

Allele description [Variation Report for NM_000088.4(COL1A1):c.387del (p.Gly130fs)]

NM_000088.4(COL1A1):c.387del (p.Gly130fs)

Gene:

COL1A1:collagen type I alpha 1 chain [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

17q21.33

Genomic location:

Preferred name:

NM_000088.4(COL1A1):c.387del (p.Gly130fs)

HGVS:

NC_000017.11:g.50199310del
NG_007400.1:g.7330del
NM_000088.4:c.387delMANE SELECT
NP_000079.2:p.Gly130fs
LRG_1:g.7330del
NC_000017.10:g.48276671del
NM_000088.3:c.387delT

Protein change:

G130fs

Links:

dbSNP: rs1555575086

NCBI 1000 Genomes Browser:

rs1555575086

Molecular consequence:

NM_000088.4:c.387del - frameshift variant - [Sequence Ontology: SO:0001589]

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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Rattus norvegicus hyaluronan and proteoglycan link protein 1 (Hapln1), mRNA
Rattus norvegicus hyaluronan and proteoglycan link protein 1 (Hapln1), mRNA
gi|119508807|ref|NM_019189.2|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000627252	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 10, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 31363794, 7942841, 9295084, 9443882, 28492532
SCV004013463	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31363794, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000627252

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 10, 2022)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV004013463

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

unknown

clinical testing

PubMed (2)
[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	unknown	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	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 (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000627252.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

ClinVar contains an entry for this variant (Variation ID: 456780). For these reasons, this variant has been classified as Pathogenic. This variant is also known as p.Pro129Profs*30. This premature translational stop signal has been observed in individual(s) with clinical features of osteogenesis imperfecta (PMID: 31363794). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gly130Alafs*135) 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).

#	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 3billion, SCV004013463.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (2)

Description

The variant is not observed in the gnomAD v2.1.1 dataset. This frameshift variant is predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported to be associated with COL1A1-related disorder (ClinVar ID: VCV000456780/PMID: 31363794). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.

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

Last Updated: Sep 29, 2024

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