NM_000088.4(COL1A1):c.1003G>A (p.Gly335Ser) AND Osteogenesis imperfecta type I

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 23, 2021
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:: RCV001388124.7

Allele description [Variation Report for NM_000088.4(COL1A1):c.1003G>A (p.Gly335Ser)]

NM_000088.4(COL1A1):c.1003G>A (p.Gly335Ser)

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.1003G>A (p.Gly335Ser)

HGVS:

NC_000017.11:g.50195976C>T
NG_007400.1:g.10664G>A
NM_000088.4:c.1003G>AMANE SELECT
NP_000079.2:p.Gly335Ser
LRG_1:g.10664G>A
NC_000017.10:g.48273337C>T

Protein change:

G335S

Links:

dbSNP: rs2144579011

NCBI 1000 Genomes Browser:

rs2144579011

Molecular consequence:

NM_000088.4:c.1003G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV001588993	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 23, 2021)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 30614853, 7695699, 8218237, 19344236, 9016532, 17078022, 31737030, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001588993

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 23, 2021)

germline

clinical testing

PubMed (8)
[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

Genotype-phenotype relationship in a large cohort of osteogenesis imperfecta patients with COL1A1 mutations revealed by a new scoring system.

Li LJ, Lyu F, Song YW, Wang O, Jiang Y, Xia WB, Xing XP, Li M.

Chin Med J (Engl). 2019 Jan 20;132(2):145-153. doi: 10.1097/CM9.0000000000000013.

PubMed [citation]

PMID:: 30614853
PMCID:: PMC6365277

Crystal and molecular structure of a collagen-like peptide at 1.9 A resolution.

Bella J, Eaton M, Brodsky B, Berman HM.

Science. 1994 Oct 7;266(5182):75-81.

PubMed [citation]

PMID:: 7695699

See all PubMed Citations (8)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001588993.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

This variant has been observed in individual(s) with autosomal dominant osteogenesis imperfecta (PMID: 30614853). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with serine at codon 335 of the COL1A1 protein (p.Gly335Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C55"). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the triple helix domain of COL1A1. Glycine residues within the Gly-Xaa-Yaa repeats of the triple helix domain are required for the structure and stability of fibrillar collagens (PMID: 7695699, 8218237, 19344236). In COL1A1, variants affecting these glycine residues are significantly enriched in individuals with disease (PMID: 9016532, 17078022) compared to the general population (ExAC). Experimental studies have shown that this variant does not affect mRNA splicing (PMID: 31737030).

#	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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