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NM_000092.5(COL4A4):c.2242G>A (p.Gly748Ser) AND COL4A4-related disorder

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 10, 2024
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV004737944.1

Allele description [Variation Report for NM_000092.5(COL4A4):c.2242G>A (p.Gly748Ser)]

NM_000092.5(COL4A4):c.2242G>A (p.Gly748Ser)

Gene:
COL4A4:collagen type IV alpha 4 chain [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q36.3
Genomic location:
Preferred name:
NM_000092.5(COL4A4):c.2242G>A (p.Gly748Ser)
HGVS:
  • NC_000002.12:g.227059546C>T
  • NG_011592.1:g.110014G>A
  • NM_000092.5:c.2242G>AMANE SELECT
  • NP_000083.3:p.Gly748Ser
  • NP_000083.3:p.Gly748Ser
  • LRG_231t1:c.2242G>A
  • LRG_231:g.110014G>A
  • LRG_231p1:p.Gly748Ser
  • NC_000002.11:g.227924262C>T
  • NM_000092.4:c.2242G>A
Protein change:
G748S
Links:
dbSNP: rs762139460
NCBI 1000 Genomes Browser:
rs762139460
Molecular consequence:
  • NM_000092.5:c.2242G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
COL4A4-related disorder
Identifiers:

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV005360865PreventionGenetics, part of Exact Sciences
no assertion criteria provided
Pathogenic
(Jun 10, 2024) 		germlineclinical testing

Help

Summary from all submissions

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

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV005360865.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The COL4A4 c.2242G>A variant is predicted to result in the amino acid substitution p.Gly748Ser. The Gly748Ser variant affects a Gly residue of the conserved triple helical domain (residues 65 – 1459) of the COL4A4 protein (uniprot.org). The majority of pathogenic variants in COL4A4 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/). This variant was reported in two individuals with focal segmental glomerulosclerosis and was shown to segregate with disease in one family (Papazachariou et al 2017. PubMed ID: 28632965). At PreventionGenetics, we have observed this variant in the heterozygous state in four individuals with COL4A4-related phenotypes and it segregated with disease in one family (Internal Data). This variant is reported in 0.0097% of alleles in individuals of Ashkenazi Jewish descent in gnomAD. This variant is interpreted as pathogenic.

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

Last Updated: Feb 25, 2025