NM_000093.5(COL5A1):c.4597C>G (p.Pro1533Ala) AND Ehlers-Danlos syndrome, classic type, 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 25, 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:: RCV002034511.6

Allele description [Variation Report for NM_000093.5(COL5A1):c.4597C>G (p.Pro1533Ala)]

NM_000093.5(COL5A1):c.4597C>G (p.Pro1533Ala)

Genes:

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

Variant type:

single nucleotide variant

Cytogenetic location:

9q34.3

Genomic location:

Preferred name:

NM_000093.5(COL5A1):c.4597C>G (p.Pro1533Ala)

HGVS:

NC_000009.12:g.134822139C>G
NG_008030.1:g.185334C>G
NM_000093.5:c.4597C>GMANE SELECT
NM_001278074.1:c.4597C>G
NP_000084.3:p.Pro1533Ala
NP_001265003.1:p.Pro1533Ala
LRG_737t2:c.4597C>G
LRG_737:g.185334C>G
LRG_737p2:p.Pro1533Ala
NC_000009.11:g.137713985C>G
NM_000093.3:c.4597C>G

Protein change:

P1533A

Links:

dbSNP: rs1839028918

NCBI 1000 Genomes Browser:

rs1839028918

Molecular consequence:

NM_000093.5:c.4597C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001278074.1:c.4597C>G - missense variant - [Sequence Ontology: SO:0001583]

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002195685	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 25, 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

SCV002195685

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 25, 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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002195685.3

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

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 COL5A1 protein function. This variant has not been reported in the literature in individuals with COL5A1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with alanine at codon 1533 of the COL5A1 protein (p.Pro1533Ala). The proline residue is highly conserved and there is a small physicochemical difference between proline and alanine.

#	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 29, 2024

ClinVar

Relating variation to medicine