NM_000093.5(COL5A1):c.1754C>T (p.Pro585Leu) AND Ehlers-Danlos syndrome, classic type

delete

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 30, 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:: RCV000686648.3

Allele description

NM_000093.5(COL5A1):c.1754C>T (p.Pro585Leu)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

9q34.3

Genomic location:

Preferred name:

NM_000093.5(COL5A1):c.1754C>T (p.Pro585Leu)

HGVS:

NC_000009.12:g.134753884C>T
NG_008030.1:g.117079C>T
NM_000093.5:c.1754C>TMANE SELECT
NM_001278074.1:c.1754C>T
NP_000084.3:p.Pro585Leu
NP_000084.3:p.Pro585Leu
NP_001265003.1:p.Pro585Leu
LRG_737t1:c.1754C>T
LRG_737t2:c.1754C>T
LRG_737:g.117079C>T
LRG_737p1:p.Pro585Leu
LRG_737p2:p.Pro585Leu
NC_000009.11:g.137645730C>T
NM_000093.3:c.1754C>T
NM_000093.4:c.1754C>T

Protein change:

P585L

Links:

dbSNP: rs530442560

NCBI 1000 Genomes Browser:

rs530442560

Molecular consequence:

NM_000093.5:c.1754C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001278074.1:c.1754C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Ehlers-Danlos syndrome, classic type (cEDS)
Identifiers:: MONDO: MONDO:0007522; MedGen: C4225429; Orphanet: 287

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000814176	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 30, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000814176

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 30, 2020)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000814176.3

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

Description

This sequence change replaces proline with leucine at codon 585 of the COL5A1 protein (p.Pro585Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs530442560, ExAC 0.03%). This variant has not been reported in the literature in individuals with COL5A1-related disease. ClinVar contains an entry for this variant (Variation ID: 264062). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C0). 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.

#	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: Apr 23, 2022

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