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NM_001845.6(COL4A1):c.1702G>T (p.Gly568Cys) AND COL4A1 or COL4A2-related cerebral small vessel disease

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jul 1, 2022
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:
RCV003225188.8

Allele description [Variation Report for NM_001845.6(COL4A1):c.1702G>T (p.Gly568Cys)]

NM_001845.6(COL4A1):c.1702G>T (p.Gly568Cys)

Gene:
COL4A1:collagen type IV alpha 1 chain [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
13q34
Genomic location:
Preferred name:
NM_001845.6(COL4A1):c.1702G>T (p.Gly568Cys)
HGVS:
  • NC_000013.11:g.110187164C>A
  • NG_011544.2:g.124986G>T
  • NM_001845.6:c.1702G>TMANE SELECT
  • NP_001836.3:p.Gly568Cys
  • LRG_1116t1:c.1702G>T
  • LRG_1116:g.124986G>T
  • LRG_1116p1:p.Gly568Cys
  • NC_000013.10:g.110839511C>A
  • NM_001845.5:c.1702G>T
Protein change:
G568C
Links:
dbSNP: rs375477517
NCBI 1000 Genomes Browser:
rs375477517
Molecular consequence:
  • NM_001845.6:c.1702G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
COL4A1 or COL4A2-related cerebral small vessel disease
Identifiers:
MedGen: C5680103

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003921925Victorian Clinical Genetics Services, Murdoch Childrens Research Institute
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Jul 1, 2022) 		paternalclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedpaternalyesnot providednot providednot providednot providednot providedclinical 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 Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV003921925.1

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

Description

0103 - Dominant negative and loss of function are likely mechanisms of disease in this gene and are associated with COL4A1-related disorders. Missense variants affecting the glycine of the triple helix of collagen genes typically exert a dominant-negative effect however, functional evidence proving this for COL4A1 is lacking (PMID: 16159887). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0112 - The condition associated with this gene has incomplete penetrance (PMID: 30413629, 21625620). (I) 0200 - Variant is predicted to result in a missense amino acid change from glycine to cysteine. (I) 0251 - This variant is heterozygous. (I) 0302 - Variant is present in gnomAD (v2 & v3) <0.001 for a dominant condition (3 heterozygotes, 0 homozygotes). (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 repeat motif (NCBI Conserved domain, PMID: 1867713). (SP) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0803 - This variant has limited previous evidence of pathogenicity in an unrelated individual. This variant is reported in ClinVar once as likely pathogenic. (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) 1206 - This variant has been shown to be paternally inherited (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

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

Last Updated: Oct 26, 2024