U.S. flag

An official website of the United States government

NM_000090.4(COL3A1):c.1165A>T (p.Asn389Tyr) AND Ehlers-Danlos syndrome, type 4

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Jan 27, 2024
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:
RCV000465133.17

Allele description [Variation Report for NM_000090.4(COL3A1):c.1165A>T (p.Asn389Tyr)]

NM_000090.4(COL3A1):c.1165A>T (p.Asn389Tyr)

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.1165A>T (p.Asn389Tyr)
Other names:
p.N389Y:AAT>TAT
HGVS:
  • NC_000002.12:g.188994053A>T
  • NG_007404.1:g.24681A>T
  • NM_000090.4:c.1165A>TMANE SELECT
  • NP_000081.1:p.Asn389Tyr
  • NP_000081.2:p.Asn389Tyr
  • LRG_3t1:c.1165A>T
  • LRG_3:g.24681A>T
  • LRG_3p1:p.Asn389Tyr
  • NC_000002.11:g.189858779A>T
  • NM_000090.3:c.1165A>T
Protein change:
N389Y
Links:
dbSNP: rs200394946
NCBI 1000 Genomes Browser:
rs200394946
Molecular consequence:
  • NM_000090.4:c.1165A>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
23

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

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000541785Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Jan 27, 2024)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV004826885All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)
Uncertain Significance
(Dec 13, 2023)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown23not providednot provided108544not providedclinical testing

Citations

PubMed

How common are single gene mutations as a cause for lacunar stroke? A targeted gene panel study.

Tan RYY, Traylor M, Megy K, Duarte D, Deevi SVV, Shamardina O, Mapeta RP; NIHR BioResource: Rare Diseases Consortium, Ouwehand WH, Gräf S, Downes K, Markus HS.

Neurology. 2019 Nov 26;93(22):e2007-e2020. doi: 10.1212/WNL.0000000000008544. Epub 2019 Nov 12.

PubMed [citation]
PMID:
31719132
PMCID:
PMC6913325

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
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000541785.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces asparagine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 389 of the COL3A1 protein (p.Asn389Tyr). This variant is present in population databases (rs200394946, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of Ehlers-Danlos syndrome or stroke (PMID: 25758994, 31719132). ClinVar contains an entry for this variant (Variation ID: 199718). 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 with a negative predictive value of 95%. 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.

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

From All of Us Research Program, National Institutes of Health, SCV004826885.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided23not providednot providedclinical testing PubMed (2)

Description

This missense variant replaces asparagine with tyrosine at codon 389 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 performed for this variant. This variant has been reported in an individual affected with possible vascular Ehlers-Danlos syndrome (PMID: 25758994). This variant has been identified in 28/282770 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown108544not providednot provided23not providednot providednot provided

Last Updated: Nov 24, 2024