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NM_033380.3(COL4A5):c.511G>A (p.Gly171Ser) AND not provided

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Dec 3, 2021
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:
RCV001963996.4

Allele description [Variation Report for NM_033380.3(COL4A5):c.511G>A (p.Gly171Ser)]

NM_033380.3(COL4A5):c.511G>A (p.Gly171Ser)

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.511G>A (p.Gly171Ser)
HGVS:
  • NC_000023.11:g.108573619G>A
  • NG_011977.2:g.138696G>A
  • NM_000495.5:c.511G>A
  • NM_033380.3:c.511G>AMANE SELECT
  • NP_000486.1:p.Gly171Ser
  • NP_203699.1:p.Gly171Ser
  • LRG_232t1:c.511G>A
  • LRG_232t2:c.511G>A
  • LRG_232:g.138696G>A
  • LRG_232p1:p.Gly171Ser
  • LRG_232p2:p.Gly171Ser
  • NC_000023.10:g.107816849G>A
Protein change:
G171S
Links:
dbSNP: rs1556404027
NCBI 1000 Genomes Browser:
rs1556404027
Molecular consequence:
  • NM_000495.5:c.511G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_033380.3:c.511G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002256619Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Dec 3, 2021) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Crystal and molecular structure of a collagen-like peptide at 1.9 A resolution.

Bella J, Eaton M, Brodsky B, Berman HM.

Science. 1994 Oct 7;266(5182):75-81.

PubMed [citation]
PMID:
7695699

Characterization of collagen-like peptides containing interruptions in the repeating Gly-X-Y sequence.

Long CG, Braswell E, Zhu D, Apigo J, Baum J, Brodsky B.

Biochemistry. 1993 Nov 2;32(43):11688-95.

PubMed [citation]
PMID:
8218237
See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002256619.3

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

Description

This missense change has been observed in individual(s) with clinical features of Alport syndrome (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 171 of the COL4A5 protein (p.Gly171Ser). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the triple helix domain of COL4A5. 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). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt COL4A5 protein function.

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

Last Updated: Sep 29, 2024