NM_000090.4(COL3A1):c.560C>T (p.Thr187Ile) AND Ehlers-Danlos syndrome, type 4

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 26, 2020
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:: RCV000698663.4

Allele description

NM_000090.4(COL3A1):c.560C>T (p.Thr187Ile)

Gene:

COL3A1:collagen type III alpha 1 chain [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q32.2

Genomic location:

Preferred name:

NM_000090.4(COL3A1):c.560C>T (p.Thr187Ile)

Other names:

p.T187I:ACA>ATA

HGVS:

NC_000002.12:g.188988112C>T
NG_007404.1:g.18740C>T
NM_000090.4:c.560C>TMANE SELECT
NP_000081.1:p.Thr187Ile
NP_000081.2:p.Thr187Ile
LRG_3t1:c.560C>T
LRG_3:g.18740C>T
LRG_3p1:p.Thr187Ile
NC_000002.11:g.189852838C>T
NM_000090.3:c.560C>T

Protein change:

T187I

Links:

dbSNP: rs371583734

NCBI 1000 Genomes Browser:

rs371583734

Molecular consequence:

NM_000090.4:c.560C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Ehlers-Danlos syndrome, type 4 (EDSVASC)
Synonyms:: Ehlers-Danlos syndrome vascular type; Ehlers Danlos syndrome, ecchymotic type; Ehlers Danlos syndrome, arterial type; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0017314; MedGen: C0268338; Orphanet: 286; OMIM: 130050

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000827343	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 26, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25944730, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000827343

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 26, 2020)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Clinical utility of a next generation sequencing panel assay for Marfan and Marfan-like syndromes featuring aortopathy.

Wooderchak-Donahue W, VanSant-Webb C, Tvrdik T, Plant P, Lewis T, Stocks J, Raney JA, Meyers L, Berg A, Rope AF, Yetman AT, Bleyl SB, Mesley R, Bull DA, Collins RT, Ojeda MM, Roberts A, Lacro R, Woerner A, Stoler J, Bayrak-Toydemir P.

Am J Med Genet A. 2015 Aug;167A(8):1747-57. doi: 10.1002/ajmg.a.37085. Epub 2015 May 5.

PubMed [citation]

PMID:: 25944730

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000827343.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces threonine with isoleucine at codon 187 of the COL3A1 protein (p.Thr187Ile). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is present in population databases (rs371583734, ExAC 0.07%). This variant has been observed in an individual affected with Marfan syndrome (PMID: 25944730). ClinVar contains an entry for this variant (Variation ID: 199711). 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 C0). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Apr 23, 2022

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