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NM_000088.4(COL1A1):c.1462G>A (p.Gly488Ser) AND Osteogenesis imperfecta type I

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Apr 7, 2022
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:
RCV000547846.10

Allele description [Variation Report for NM_000088.4(COL1A1):c.1462G>A (p.Gly488Ser)]

NM_000088.4(COL1A1):c.1462G>A (p.Gly488Ser)

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.1462G>A (p.Gly488Ser)
HGVS:
  • NC_000017.11:g.50194626C>T
  • NG_007400.1:g.12014G>A
  • NM_000088.4:c.1462G>AMANE SELECT
  • NP_000079.2:p.Gly488Ser
  • NP_000079.2:p.Gly488Ser
  • LRG_1t1:c.1462G>A
  • LRG_1:g.12014G>A
  • LRG_1p1:p.Gly488Ser
  • NC_000017.10:g.48271987C>T
  • NM_000088.3:c.1462G>A
Protein change:
G488S
Links:
dbSNP: rs1328384458
NCBI 1000 Genomes Browser:
rs1328384458
Molecular consequence:
  • NM_000088.4:c.1462G>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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000627178Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Apr 7, 2022) 		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

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

Characterization of collagen-like peptides containing interruptions in the repeating Gly-X-Y sequence.

Long CG, Braswell E, Zhu D, Apigo J, Baum J, Brodsky B.

Biochemistry. 1993 Nov 2;32(43):11688-95.

PubMed [citation]
PMID:
8218237
See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000627178.7

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

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely 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). 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"). ClinVar contains an entry for this variant (Variation ID: 452610). This variant has not been reported in the literature in individuals affected with COL1A1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 488 of the COL1A1 protein (p.Gly488Ser).

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

Last Updated: Sep 29, 2024