U.S. flag

An official website of the United States government

NM_033380.3(COL4A5):c.3704G>T (p.Gly1235Val) AND X-linked Alport syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 21, 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:
RCV001252965.4

Allele description [Variation Report for NM_033380.3(COL4A5):c.3704G>T (p.Gly1235Val)]

NM_033380.3(COL4A5):c.3704G>T (p.Gly1235Val)

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.3704G>T (p.Gly1235Val)
HGVS:
  • NC_000023.11:g.108668418G>T
  • NG_011977.2:g.233495G>T
  • NM_000495.5:c.3704G>T
  • NM_033380.2:c.3704G>T
  • NM_033380.3:c.3704G>TMANE SELECT
  • NP_000486.1:p.Gly1235Val
  • NP_203699.1:p.Gly1235Val
  • LRG_232t1:c.3704G>T
  • LRG_232t2:c.3704G>T
  • LRG_232:g.233495G>T
  • LRG_232p1:p.Gly1235Val
  • LRG_232p2:p.Gly1235Val
  • NC_000023.10:g.107911648G>T
  • NG_011977.1:g.233495G>T
  • NM_000495.4:c.3704G>T
  • NM_033380.1:c.3704G>T
Protein change:
G1235V
Links:
dbSNP: rs2068130178
NCBI 1000 Genomes Browser:
rs2068130178
Molecular consequence:
  • NM_000495.5:c.3704G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_033380.3:c.3704G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
X-linked Alport syndrome (ATS1)
Synonyms:
NEPHROPATHY AND DEAFNESS, X-LINKED; Alport syndrome 1, X-linked recessive; Alport Syndrome and Thin Basement Membrane Nephropathy
Identifiers:
MONDO: MONDO:0010520; MedGen: C4746986; Orphanet: 63; Orphanet: 88917; OMIM: 301050

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001427131Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Dec 21, 2023) 		germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

COL4A3/COL4A4 mutations: from familial hematuria to autosomal-dominant or recessive Alport syndrome.

Longo I, Porcedda P, Mari F, Giachino D, Meloni I, Deplano C, Brusco A, Bosio M, Massella L, Lavoratti G, Roccatello D, Frascá G, Mazzucco G, Muda AO, Conti M, Fasciolo F, Arrondel C, Heidet L, Renieri A, De Marchi M.

Kidney Int. 2002 Jun;61(6):1947-56.

PubMed [citation]
PMID:
12028435

Alport retinopathy results from "severe" COL4A5 mutations and predicts early renal failure.

Tan R, Colville D, Wang YY, Rigby L, Savige J.

Clin J Am Soc Nephrol. 2010 Jan;5(1):34-8. doi: 10.2215/CJN.01030209. Epub 2009 Dec 3.

PubMed [citation]
PMID:
19965530
PMCID:
PMC2801648
See all PubMed Citations (6)

Details of each submission

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV001427131.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. The following criteria are met: 0103 - Dominant negative and loss of function are known mechanisms of disease in this gene and are associated with X-linked Alport syndrome 1 (MIM#301050). Dominant negative is caused mostly by glycine substitutions that affect the conformation of the protein, and loss of function can be caused by either protein truncating or missense variants (PMID: 24046192, 12028435). (I) 0110 - This gene is associated with X-linked dominant disease. Males are typically more severely affected than females (PMID: 19965530). (I) 0200 - Variant is predicted to result in a missense amino acid change from glycine to valine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0601 - Variant is located in the well-established functional Gly-X-Y motif and affects a glycine residue (DECIPHER). (SP) 0702 - Other missense variants comparable to the one identified in this case have strong previous evidence for pathogenicity. p.(Gly1235Ala) was identified in two unrelated males with X-linked Alport syndrome (PMID: 30577881, 37097554). p.(Gly1235Asp) was identified in one male with X-linked Alport syndrome (PMID: 30577881), and has been classified as pathogenic or likely pathogenic (LOVD). p.(Gly1235Cys) has been classified as likely pathogenic by a clinical laboratory in ClinVar. (SP) 0803 - This variant has limited previous evidence of pathogenicity in an unrelated individual. This variant was classified as pathogenic by a clinical laboratory in ClinVar. (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Aug 4, 2024