NM_000090.4(COL3A1):c.1173del (p.Pro392fs) AND Ehlers-Danlos syndrome, type 4

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Oct 17, 2017
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:: RCV000616357.4

Allele description [Variation Report for NM_000090.4(COL3A1):c.1173del (p.Pro392fs)]

NM_000090.4(COL3A1):c.1173del (p.Pro392fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

2q32.2

Genomic location:

Preferred name:

NM_000090.4(COL3A1):c.1173del (p.Pro392fs)

HGVS:

NC_000002.12:g.188994061del
NG_007404.1:g.24689del
NM_000090.4:c.1173delMANE SELECT
NP_000081.2:p.Pro392fs
LRG_3:g.24689del
NC_000002.11:g.189858787del
NC_000002.11:g.189858787delT
NM_000090.3:c.1173delT
p.Pro392LeufsX18

Protein change:

P392fs

Links:

dbSNP: rs1553507863

NCBI 1000 Genomes Browser:

rs1553507863

Molecular consequence:

NM_000090.4:c.1173del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

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
SCV000731732	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Likely pathogenic (Oct 17, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 28349240, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000731732

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Likely pathogenic
(Oct 17, 2017)

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	not provided	1	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

The Human Gene Mutation Database: towards a comprehensive repository of inherited mutation data for medical research, genetic diagnosis and next-generation sequencing studies.

Stenson PD, Mort M, Ball EV, Evans K, Hayden M, Heywood S, Hussain M, Phillips AD, Cooper DN.

Hum Genet. 2017 Jun;136(6):665-677. doi: 10.1007/s00439-017-1779-6. Epub 2017 Mar 27. Review.

PubMed [citation]

PMID:: 28349240
PMCID:: PMC5429360

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000731732.1

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

Description

The p.Pro392fs variant in COL3A1 has not been previously reported in individuals with Ehlers-Danlos Syndrome (EDS) and was absent from large population studies, though the ability of these studies to accurately detect indels may be limited. This variant is predicted to cause a frameshift, which alters the protein?s ami no acid sequence beginning at position 392 and leads to a premature termination codon 18 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Frameshift and other loss of function variants have been reported in association with EDS in the HGMD database (Stenson, 2017). In summary, although additional studies are required to fully establish its clinica l significance, the p.Pro392fs variant is likely pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		1	not provided	1	not provided

Last Updated: Jun 2, 2024

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