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NM_212482.4(FN1):c.367T>C (p.Cys123Arg) AND not provided

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jul 1, 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:
RCV002526994.2

Allele description [Variation Report for NM_212482.4(FN1):c.367T>C (p.Cys123Arg)]

NM_212482.4(FN1):c.367T>C (p.Cys123Arg)

Gene:
FN1:fibronectin 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q35
Genomic location:
Preferred name:
NM_212482.4(FN1):c.367T>C (p.Cys123Arg)
HGVS:
  • NC_000002.12:g.215433372A>G
  • NG_012196.1:g.7697T>C
  • NM_001306129.2:c.367T>C
  • NM_001306130.2:c.367T>C
  • NM_001306131.2:c.367T>C
  • NM_001306132.2:c.367T>C
  • NM_001365517.2:c.367T>C
  • NM_001365518.2:c.367T>C
  • NM_001365519.2:c.367T>C
  • NM_001365520.2:c.367T>C
  • NM_001365521.2:c.367T>C
  • NM_001365522.2:c.367T>C
  • NM_001365523.2:c.367T>C
  • NM_001365524.2:c.367T>C
  • NM_002026.4:c.367T>C
  • NM_054034.3:c.367T>C
  • NM_212474.3:c.367T>C
  • NM_212476.3:c.367T>C
  • NM_212478.3:c.367T>C
  • NM_212482.4:c.367T>CMANE SELECT
  • NP_001293058.2:p.Cys123Arg
  • NP_001293059.2:p.Cys123Arg
  • NP_001293060.2:p.Cys123Arg
  • NP_001293061.2:p.Cys123Arg
  • NP_001352446.1:p.Cys123Arg
  • NP_001352447.1:p.Cys123Arg
  • NP_001352448.1:p.Cys123Arg
  • NP_001352449.1:p.Cys123Arg
  • NP_001352450.1:p.Cys123Arg
  • NP_001352451.1:p.Cys123Arg
  • NP_001352452.1:p.Cys123Arg
  • NP_001352453.1:p.Cys123Arg
  • NP_002017.2:p.Cys123Arg
  • NP_473375.2:p.Cys123Arg
  • NP_997639.2:p.Cys123Arg
  • NP_997641.2:p.Cys123Arg
  • NP_997643.2:p.Cys123Arg
  • NP_997647.2:p.Cys123Arg
  • NC_000002.11:g.216298095A>G
  • NC_000002.11:g.216298095A>G
  • NM_212482.2:c.367T>C
Protein change:
C123R; CYS123ARG
Links:
OMIM: 135600.0006; dbSNP: rs1553667072
NCBI 1000 Genomes Browser:
rs1553667072
Molecular consequence:
  • NM_001306129.2:c.367T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001306130.2:c.367T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001306131.2:c.367T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001306132.2:c.367T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365517.2:c.367T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365518.2:c.367T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365519.2:c.367T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365520.2:c.367T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365521.2:c.367T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365522.2:c.367T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365523.2:c.367T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365524.2:c.367T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002026.4:c.367T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_054034.3:c.367T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_212474.3:c.367T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_212476.3:c.367T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_212478.3:c.367T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_212482.4:c.367T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV003524898Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Jul 1, 2022)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Mutations in Fibronectin Cause a Subtype of Spondylometaphyseal Dysplasia with "Corner Fractures".

Lee CS, Fu H, Baratang N, Rousseau J, Kumra H, Sutton VR, Niceta M, Ciolfi A, Yamamoto G, Bertola D, Marcelis CL, Lugtenberg D, Bartuli A, Kim C, Hoover-Fong J, Sobreira N, Pauli R, Bacino C, Krakow D, Parboosingh J, Yap P, Kariminejad A, et al.

Am J Hum Genet. 2017 Nov 2;101(5):815-823. doi: 10.1016/j.ajhg.2017.09.019.

PubMed [citation]
PMID:
29100092
PMCID:
PMC5673654

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV003524898.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. 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: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). ClinVar contains an entry for this variant (Variation ID: 424644). This missense change has been observed in individual(s) with spondylometaphyseal dysplasia, 'corner fracture' type (PMID: 29100092). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 123 of the FN1 protein (p.Cys123Arg).

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

Last Updated: Feb 14, 2024