NM_212482.4(FN1):c.638G>A (p.Cys213Tyr) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Apr 13, 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:: RCV001796767.7

Allele description [Variation Report for NM_212482.4(FN1):c.638G>A (p.Cys213Tyr)]

NM_212482.4(FN1):c.638G>A (p.Cys213Tyr)

Gene:

FN1:fibronectin 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q35

Genomic location:

Preferred name:

NM_212482.4(FN1):c.638G>A (p.Cys213Tyr)

HGVS:

NC_000002.12:g.215430762C>T
NG_012196.1:g.10307G>A
NM_001306129.2:c.638G>A
NM_001306130.2:c.638G>A
NM_001306131.2:c.638G>A
NM_001306132.2:c.638G>A
NM_001365517.2:c.638G>A
NM_001365518.2:c.638G>A
NM_001365519.2:c.638G>A
NM_001365520.2:c.638G>A
NM_001365521.2:c.638G>A
NM_001365522.2:c.638G>A
NM_001365523.2:c.638G>A
NM_001365524.2:c.638G>A
NM_002026.4:c.638G>A
NM_054034.3:c.638G>A
NM_212474.3:c.638G>A
NM_212476.3:c.638G>A
NM_212478.3:c.638G>A
NM_212482.4:c.638G>AMANE SELECT
NP_001293058.2:p.Cys213Tyr
NP_001293059.2:p.Cys213Tyr
NP_001293060.2:p.Cys213Tyr
NP_001293061.2:p.Cys213Tyr
NP_001352446.1:p.Cys213Tyr
NP_001352447.1:p.Cys213Tyr
NP_001352448.1:p.Cys213Tyr
NP_001352449.1:p.Cys213Tyr
NP_001352450.1:p.Cys213Tyr
NP_001352451.1:p.Cys213Tyr
NP_001352452.1:p.Cys213Tyr
NP_001352453.1:p.Cys213Tyr
NP_002017.2:p.Cys213Tyr
NP_473375.2:p.Cys213Tyr
NP_997639.2:p.Cys213Tyr
NP_997641.2:p.Cys213Tyr
NP_997643.2:p.Cys213Tyr
NP_997647.2:p.Cys213Tyr
NC_000002.11:g.216295485C>T
NM_212482.2:c.638G>A

Protein change:

C213Y

Links:

dbSNP: rs1559604072

Molecular consequence:

NM_001306129.2:c.638G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001306130.2:c.638G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001306131.2:c.638G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001306132.2:c.638G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001365517.2:c.638G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001365518.2:c.638G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001365519.2:c.638G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001365520.2:c.638G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001365521.2:c.638G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001365522.2:c.638G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001365523.2:c.638G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001365524.2:c.638G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_002026.4:c.638G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_054034.3:c.638G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_212474.3:c.638G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_212476.3:c.638G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_212478.3:c.638G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_212482.4:c.638G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002037270	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Uncertain significance	germline	clinical testing
SCV002038224	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Uncertain significance	germline	clinical testing
SCV003483363	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 13, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30599297, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002037270

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus

See additional submitters

no assertion criteria provided

Uncertain significance

germline

clinical testing

SCV002038224

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus

See additional submitters

no assertion criteria provided

Uncertain significance

germline

clinical testing

SCV003483363

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 13, 2022)

germline

clinical testing

PubMed (2)
[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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Novel fibronectin mutations and expansion of the phenotype in spondylometaphyseal dysplasia with "corner fractures".

Costantini A, Valta H, Baratang NV, Yap P, Bertola DR, Yamamoto GL, Kim CA, Chen J, Wierenga KJ, Fanning EA, Escobar L, McWalter K, McLaughlin H, Willaert R, Begtrup A, Alm JJ, Reinhardt DP, Mäkitie O, Campeau PM.

Bone. 2019 Apr;121:163-171. doi: 10.1016/j.bone.2018.12.020. Epub 2018 Dec 30.

PubMed [citation]

PMID:: 30599297

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 Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus, SCV002037270.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV002038224.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003483363.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical 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: 549707). This missense change has been observed in individual(s) with FN1-related conditions (PMID: 30599297; Invitae). 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 tyrosine, which is neutral and polar, at codon 213 of the FN1 protein (p.Cys213Tyr).

#	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: Feb 15, 2026

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