NM_000090.4(COL3A1):c.560C>T (p.Thr187Ile) AND Familial thoracic aortic aneurysm and aortic dissection

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Dec 20, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001190472.6

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

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:: Familial thoracic aortic aneurysm and aortic dissection (TAAD)
Synonyms:: Thoracic aortic aneurysm and aortic dissection; Thoracic aortic aneurysms and dissections
Identifiers:: MONDO: MONDO:0019625; MedGen: C4707243; Orphanet: 91387; OMIM: PS607086

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001357972	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Dec 20, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25944730, 25741868
SCV002651441	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Jun 17, 2021)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001357972

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Dec 20, 2022)

germline

clinical testing

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

SCV002651441

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Jun 17, 2021)

germline

clinical testing

Citation Link

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001357972.3

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

Description

This missense variant replaces threonine with isoleucine at codon 187 of the COL3A1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with Marfan syndrome (PMID: 25944730). This variant has been identified in 12/282348 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is 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

From Ambry Genetics, SCV002651441.2

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

Description

The c.560C>T (p.T187I) alteration is located in exon 6 (coding exon 6) of the COL3A1 gene. This alteration results from a C to T substitution at nucleotide position 560, causing the threonine (T) at amino acid position 187 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

#	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: Nov 24, 2024

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