NM_033380.3(COL4A5):c.4342G>T (p.Gly1448Cys) AND COL4A5-related disorder

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Oct 3, 2023
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:: RCV003400415.5

Allele description [Variation Report for NM_033380.3(COL4A5):c.4342G>T (p.Gly1448Cys)]

NM_033380.3(COL4A5):c.4342G>T (p.Gly1448Cys)

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.4342G>T (p.Gly1448Cys)

HGVS:

NC_000023.11:g.108687508G>T
NG_011977.2:g.252585G>T
NM_000495.5:c.4324G>T
NM_033380.3:c.4342G>TMANE SELECT
NP_000486.1:p.Gly1442Cys
NP_203699.1:p.Gly1448Cys
LRG_232t1:c.4324G>T
LRG_232t2:c.4342G>T
LRG_232:g.252585G>T
LRG_232p1:p.Gly1442Cys
LRG_232p2:p.Gly1448Cys
NC_000023.10:g.107930738G>T
NM_000495.4:c.4324G>T

Protein change:

G1442C

Molecular consequence:

NM_000495.5:c.4324G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_033380.3:c.4342G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: COL4A5-related disorder
Synonyms:: COL4A5-related condition
Identifiers:

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MRPL52 mitochondrial ribosomal protein L52 [Homo sapiens]
MRPL52 mitochondrial ribosomal protein L52 [Homo sapiens]
Gene ID:122704

Gene
122704[uid] AND (alive[prop]) (1)
Gene
Sleep apnea
Sleep apnea

MedGen
C0037315[conceptid] (1)
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004103931	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Oct 3, 2023)	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

SCV004103931

PreventionGenetics, part of Exact Sciences

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Oct 3, 2023)

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

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

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004103931.1

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

Description

The COL4A5 c.4324G>T variant is predicted to result in the amino acid substitution p.Gly1442Cys. The p.Gly1442 residue resides in the triple-helical region (residues 42 – 1456) of the COL4A5 protein (uniprot.org). The majority of pathogenic variants in COL4A5 substitute a glycine residue to a bulkier amino acid in the triple-helical domain (Hudson et al. 1993. PubMed ID: 8253711; https://www.ncbi.nlm.nih.gov/books/NBK1207/). Other amino acid substitutions at this position (p.Gly1442Arg, p.Gly1442Ser, p.Gly1442Asp) have been reported in individuals with COL4A5-related disorders (eg. King et al 2006. PubMed ID: 16941480; Boeckhaus et al 2021. PubMed ID: 33040356; Plant et al 1999. PubMed ID: 10094548). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted 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: Jun 23, 2024

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