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NM_000088.4(COL1A1):c.934C>T (p.Arg312Cys) AND Osteogenesis imperfecta type I

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 28, 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:
RCV000631472.13

Allele description [Variation Report for NM_000088.4(COL1A1):c.934C>T (p.Arg312Cys)]

NM_000088.4(COL1A1):c.934C>T (p.Arg312Cys)

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.934C>T (p.Arg312Cys)
Other names:
R134C
HGVS:
  • NC_000017.11:g.50196337G>A
  • NG_007400.1:g.10303C>T
  • NG_087083.1:g.97G>A
  • NM_000088.4:c.934C>TMANE SELECT
  • NP_000079.2:p.Arg312Cys
  • NP_000079.2:p.Arg312Cys
  • LRG_1t1:c.934C>T
  • LRG_1:g.10303C>T
  • LRG_1p1:p.Arg312Cys
  • NC_000017.10:g.48273698G>A
  • NM_000088.3:c.934C>T
Protein change:
R312C; ARG134CYS
Links:
OMIM: 120150.0059; dbSNP: rs72645347
NCBI 1000 Genomes Browser:
rs72645347
Molecular consequence:
  • NM_000088.4:c.934C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Osteogenesis imperfecta type I (OI1)
Synonyms:
OI, TYPE I; OSTEOGENESIS IMPERFECTA TARDA; OSTEOGENESIS IMPERFECTA WITH BLUE SCLERAE; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0008146; MedGen: C0023931; Orphanet: 666; OMIM: 166200

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000752552Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Apr 28, 2023) 		germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Classical Ehlers-Danlos syndrome caused by a mutation in type I collagen.

Nuytinck L, Freund M, Lagae L, Pierard GE, Hermanns-Le T, De Paepe A.

Am J Hum Genet. 2000 Apr;66(4):1398-402. Epub 2000 Mar 17.

PubMed [citation]
PMID:
10739762
PMCID:
PMC1288203

Three arginine to cysteine substitutions in the pro-alpha (I)-collagen chain cause Ehlers-Danlos syndrome with a propensity to arterial rupture in early adulthood.

Malfait F, Symoens S, De Backer J, Hermanns-Lê T, Sakalihasan N, Lapière CM, Coucke P, De Paepe A.

Hum Mutat. 2007 Apr;28(4):387-95.

PubMed [citation]
PMID:
17211858
See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000752552.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 312 of the COL1A1 protein (p.Arg312Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with EDS and Ehlers-Danlos syndrome (EDS) (PMID: 10739762, 17211858, 23587214, 25597651, 28102596). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 17343). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt COL1A1 protein function. For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Apr 20, 2025