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

Clinical significance:Uncertain significance (Last evaluated: May 26, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_000090.4(COL3A1):c.560C>T (p.Thr187Ile)]

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

COL3A1:collagen type III alpha 1 chain [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000090.4(COL3A1):c.560C>T (p.Thr187Ile)
Other names:
  • NC_000002.12:g.188988112C>T
  • NG_007404.1:g.18740C>T
  • NM_000090.3:c.560C>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
Protein change:
dbSNP: rs371583734
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000090.3:c.560C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000090.4:c.560C>T - missense variant - [Sequence Ontology: SO:0001583]


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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000827343Invitaecriteria provided, single submitter
Uncertain significance
(May 26, 2020)
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



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]

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]

Details of each submission

From Invitae, SCV000827343.4

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


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.

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

Last Updated: Oct 30, 2021

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