NM_033380.3(COL4A5):c.1591_1599del (p.Ile531_Gly533del) AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 3, 2024
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:: RCV003705583.1

Allele description [Variation Report for NM_033380.3(COL4A5):c.1591_1599del (p.Ile531_Gly533del)]

NM_033380.3(COL4A5):c.1591_1599del (p.Ile531_Gly533del)

Gene:

COL4A5:collagen type IV alpha 5 chain [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

Xq22.3

Genomic location:

Preferred name:

NM_033380.3(COL4A5):c.1591_1599del (p.Ile531_Gly533del)

HGVS:

NC_000023.11:g.108597380_108597388del
NG_011977.2:g.162457_162465del
NM_000495.5:c.1591_1599del
NM_033380.3:c.1591_1599delMANE SELECT
NP_000486.1:p.Ile531_Gly533del
NP_203699.1:p.Ile531_Gly533del
LRG_232t1:c.1591_1599del
LRG_232t2:c.1591_1599del
LRG_232:g.162457_162465del
LRG_232p1:p.Ile531_Gly533del
LRG_232p2:p.Ile531_Gly533del
NC_000023.10:g.107840610_107840618del

Molecular consequence:

NM_000495.5:c.1591_1599del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_033380.3:c.1591_1599del - inframe_deletion - [Sequence Ontology: SO:0001822]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004470994	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jan 3, 2024)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 7695699, 8218237, 19344236, 23720012, 27627812, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004470994

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jan 3, 2024)

germline

clinical testing

PubMed (6)
[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

Crystal and molecular structure of a collagen-like peptide at 1.9 A resolution.

Bella J, Eaton M, Brodsky B, Berman HM.

Science. 1994 Oct 7;266(5182):75-81.

PubMed [citation]

PMID:: 7695699

Characterization of collagen-like peptides containing interruptions in the repeating Gly-X-Y sequence.

Long CG, Braswell E, Zhu D, Apigo J, Baum J, Brodsky B.

Biochemistry. 1993 Nov 2;32(43):11688-95.

PubMed [citation]

PMID:: 8218237

See all PubMed Citations (6)

Details of each submission

From Invitae, SCV004470994.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This variant, c.1591_1599del, results in the deletion of 3 amino acid(s) of the COL4A5 protein (p.Ile531_Gly533del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs768382989, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with COL4A5-related conditions. This variant disrupts the triple helix domain of COL4A5. Glycine residues within the Gly-Xaa-Yaa repeats of the triple helix domain are required for the structure and stability of fibrillar collagens (PMID: 7695699, 8218237, 19344236). In COL4A5, missense variants at these glycine residues are significantly enriched in individuals with disease (PMID: 23720012, 27627812) compared to the general population (ExAC). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

#	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: Feb 28, 2024

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