NM_000090.4(COL3A1):c.2927T>C (p.Val976Ala) 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:: Jan 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:: RCV000458398.7

Allele description

NM_000090.4(COL3A1):c.2927T>C (p.Val976Ala)

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.2927T>C (p.Val976Ala)

HGVS:

NC_000002.12:g.189004360T>C
NG_007404.1:g.34988T>C
NM_000090.4:c.2927T>CMANE SELECT
NP_000081.1:p.Val976Ala
NP_000081.2:p.Val976Ala
LRG_3t1:c.2927T>C
LRG_3:g.34988T>C
LRG_3p1:p.Val976Ala
NC_000002.11:g.189869086T>C
NM_000090.3:c.2927T>C

Protein change:

V976A

Links:

dbSNP: rs886038939

NCBI 1000 Genomes Browser:

rs886038939

Molecular consequence:

NM_000090.4:c.2927T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Ehlers-Danlos syndrome, type 4
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
SCV000541801	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 1, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29650765, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000541801

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 1, 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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Prospective Cardiovascular Genetics Evaluation in Spontaneous Coronary Artery Dissection.

Kaadan MI, MacDonald C, Ponzini F, Duran J, Newell K, Pitler L, Lin A, Weinberg I, Wood MJ, Lindsay ME.

Circ Genom Precis Med. 2018 Apr;11(4):e001933. doi: 10.1161/CIRCGENETICS.117.001933.

PubMed [citation]

PMID:: 29650765

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, SCV000541801.5

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

Description

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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt COL3A1 protein function. ClinVar contains an entry for this variant (Variation ID: 263828). This missense change has been observed in individual(s) with spontaneous coronary artery dissection (PMID: 29650765). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 976 of the COL3A1 protein (p.Val976Ala).

#	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: Sep 16, 2024

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