NM_033380.3(COL4A5):c.1607G>A (p.Gly536Asp) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Apr 10, 2021
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000684748.14

Allele description [Variation Report for NM_033380.3(COL4A5):c.1607G>A (p.Gly536Asp)]

NM_033380.3(COL4A5):c.1607G>A (p.Gly536Asp)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

Xq22.3

Genomic location:

Preferred name:

NM_033380.3(COL4A5):c.1607G>A (p.Gly536Asp)

HGVS:

NC_000023.11:g.108597396G>A
NG_011977.2:g.162473G>A
NM_000495.5:c.1607G>A
NM_033380.3:c.1607G>AMANE SELECT
NP_000486.1:p.Gly536Asp
NP_203699.1:p.Gly536Asp
LRG_232t1:c.1607G>A
LRG_232t2:c.1607G>A
LRG_232:g.162473G>A
LRG_232p1:p.Gly536Asp
LRG_232p2:p.Gly536Asp
NC_000023.10:g.107840626G>A
NG_011977.1:g.162473G>A
NM_000495.4:c.1607G>A

Protein change:

G536D

Links:

dbSNP: rs104886125

NCBI 1000 Genomes Browser:

rs104886125

Molecular consequence:

NM_000495.5:c.1607G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_033380.3:c.1607G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000809381	Gharavi Laboratory, Columbia University	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Sep 16, 2018)	germline	research	PubMed (1) [See all records that cite this PMID]
SCV001232826	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 10, 2021)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 17660027, 7695699, 8218237, 19344236, 23720012, 27627812, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000809381

Gharavi Laboratory, Columbia University

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Sep 16, 2018)

germline

research

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

SCV001232826

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 10, 2021)

germline

clinical testing

PubMed (7)
[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
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	research

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Genetic testing for X-linked Alport syndrome by direct sequencing of COL4A5 cDNA from hair root RNA samples.

Tazón-Vega B, Ars E, Burset M, Santín S, Ruíz P, Fernández-Llama P, Ballarín J, Torra R.

Am J Kidney Dis. 2007 Aug;50(2):257.e1-14.

PubMed [citation]

PMID:: 17660027

See all PubMed Citations (8)

Details of each submission

From Gharavi Laboratory, Columbia University, SCV000809381.1

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

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

From Invitae, SCV001232826.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with aspartic acid at codon 536 of the COL4A5 protein (p.Gly536Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant has been observed in individuals with Alport syndrome (PMID: 17660027, Invitae). ClinVar contains an entry for this variant (Variation ID: 24429). For these reasons, this variant has been classified as Pathogenic. 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).

#	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: May 1, 2024

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