NM_000093.5(COL5A1):c.5340dup (p.Tyr1781fs) AND Ehlers-Danlos syndrome, classic type, 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 9, 2020
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:: RCV002242885.14

Allele description [Variation Report for NM_000093.5(COL5A1):c.5340dup (p.Tyr1781fs)]

NM_000093.5(COL5A1):c.5340dup (p.Tyr1781fs)

Genes:

COL5A1:collagen type V alpha 1 chain [Gene - OMIM - HGNC]
LOC101448202:uncharacterized LOC101448202 [Gene]

Variant type:

Duplication

Cytogenetic location:

9q34.3

Genomic location:

Preferred name:

NM_000093.5(COL5A1):c.5340dup (p.Tyr1781fs)

HGVS:

NC_000009.12:g.134835174dup
NG_008030.1:g.198369dup
NM_000093.5:c.5340dupMANE SELECT
NM_001278074.1:c.5340dup
NP_000084.3:p.Tyr1781fs
NP_001265003.1:p.Tyr1781fs
LRG_737t2:c.5340dup
LRG_737:g.198369dup
LRG_737p2:p.Tyr1781fs
NC_000009.11:g.137727016_137727017insC
NC_000009.11:g.137727020dup

Protein change:

Y1781fs

Links:

dbSNP: rs2132926166

NCBI 1000 Genomes Browser:

rs2132926166

Molecular consequence:

NM_000093.5:c.5340dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001278074.1:c.5340dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Ehlers-Danlos syndrome, classic type, 1 (EDSCL1)
Synonyms:: EHLERS-DANLOS SYNDROME, GRAVIS TYPE; EHLERS-DANLOS SYNDROME, SEVERE CLASSIC TYPE; Ehlers-Danlos syndrome, type 1; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0019567; MedGen: C0268335; OMIM: 130000

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001579994	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 9, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23587214, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001579994

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 9, 2020)

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

Clinical and molecular characterization of 40 patients with classic Ehlers-Danlos syndrome: identification of 18 COL5A1 and 2 COL5A2 novel mutations.

Ritelli M, Dordoni C, Venturini M, Chiarelli N, Quinzani S, Traversa M, Zoppi N, Vascellaro A, Wischmeijer A, Manfredini E, Garavelli L, Calzavara-Pinton P, Colombi M.

Orphanet J Rare Dis. 2013 Apr 12;8:58. doi: 10.1186/1750-1172-8-58.

PubMed [citation]

PMID:: 23587214
PMCID:: PMC3653713

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001579994.4

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

Description

This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the COL5A1 protein. Other variant(s) that disrupt this region (p.Phe1820Argfs*2) have been determined to be pathogenic (PMID: 23587214). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This variant has not been reported in the literature in individuals with COL5A1-related conditions. This sequence change results in a premature translational stop signal in the COL5A1 gene (p.Tyr1781Leufs*39). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 58 amino acids of the COL5A1 protein.

#	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 3, 2024

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