NM_000088.4(COL1A1):c.432del (p.Gly145fs) AND Osteogenesis imperfecta type I

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 3, 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:: RCV001863955.6

Allele description [Variation Report for NM_000088.4(COL1A1):c.432del (p.Gly145fs)]

NM_000088.4(COL1A1):c.432del (p.Gly145fs)

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.432del (p.Gly145fs)

HGVS:

NC_000017.11:g.50199270del
NG_007400.1:g.7375del
NM_000088.3:c.432del
NM_000088.4:c.432delMANE SELECT
NP_000079.2:p.Gly145fs
LRG_1t1:c.432del
LRG_1:g.7375del
NC_000017.10:g.48276626del
NC_000017.10:g.48276631del

Protein change:

G145fs

Links:

dbSNP: rs72667016

NCBI 1000 Genomes Browser:

rs72667016

Molecular consequence:

NM_000088.4:c.432del - 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

Recent activity

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RecName: Full=Serine/threonine-protein kinase VRK2; AltName: Full=Vaccinia-relat...
RecName: Full=Serine/threonine-protein kinase VRK2; AltName: Full=Vaccinia-related kinase 2
gi|90116515|sp|Q86Y07.3|VRK2_HUMAN

Protein
kin of IRRE-like protein 2 isoform X1 [Felis catus]
kin of IRRE-like protein 2 isoform X1 [Felis catus]
gi|2131058388|ref|XP_019674254.3|

Protein
Enterobacter ludwigii strain EN-119 scaffold2, whole genome shotgun sequence
Enterobacter ludwigii strain EN-119 scaffold2, whole genome shotgun sequence
gi|748767552|ref|NZ_JTLO01000002.1| WGS:NZ_JTLO01|scaffold2

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002126024	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 3, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 16786509, 7942841, 9295084, 9443882, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002126024

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 3, 2023)

germline

clinical testing

PubMed (5)
[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

Citations

PubMed

Mutation analysis of COL1A1 and COL1A2 in patients diagnosed with osteogenesis imperfecta type I-IV.

Pollitt R, McMahon R, Nunn J, Bamford R, Afifi A, Bishop N, Dalton A.

Hum Mutat. 2006 Jul;27(7):716.

PubMed [citation]

PMID:: 16786509

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 (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002126024.3

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

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1357973). This variant is also known as p.P144fsX120. This premature translational stop signal has been observed in individual(s) with osteogenesis imperfecta (PMID: 16786509). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Gly145Aspfs*120) 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

Last Updated: Sep 29, 2024

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