NM_000091.4(COL4A3):c.1354G>A (p.Gly452Arg) AND not provided

Clinical significance:Pathogenic (Last evaluated: Aug 7, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000681919.3

Allele description [Variation Report for NM_000091.4(COL4A3):c.1354G>A (p.Gly452Arg)]

NM_000091.4(COL4A3):c.1354G>A (p.Gly452Arg)

Genes:
MFF-DT:MFF divergent transcript [Gene - HGNC]
COL4A3:collagen type IV alpha 3 chain [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q36.3
Genomic location:
Preferred name:
NM_000091.4(COL4A3):c.1354G>A (p.Gly452Arg)
HGVS:
  • NC_000002.12:g.227266455G>A
  • NG_011591.1:g.106891G>A
  • NM_000091.4:c.1354G>A
  • NP_000082.2:p.Gly452Arg
  • LRG_230t1:c.1354G>A
  • LRG_230:g.106891G>A
  • LRG_230p1:p.Gly452Arg
  • NC_000002.11:g.228131171G>A
Protein change:
G452R
Links:
dbSNP: rs772958162
NCBI 1000 Genomes Browser:
rs772958162
Molecular consequence:
  • NM_000091.4:c.1354G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000809402Gharavi Laboratory,Columbia Universityno assertion criteria provided
Likely pathogenic
(Sep 16, 2018)
germlineresearch

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

SCV001399187Invitaecriteria provided, single submitter
Pathogenic
(Aug 7, 2019)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Summary from all submissions

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

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

Natural history of genetically proven autosomal recessive Alport syndrome.

Oka M, Nozu K, Kaito H, Fu XJ, Nakanishi K, Hashimura Y, Morisada N, Yan K, Matsuo M, Yoshikawa N, Vorechovsky I, Iijima K.

Pediatr Nephrol. 2014 Sep;29(9):1535-44. doi: 10.1007/s00467-014-2797-4. Epub 2014 Mar 15.

PubMed [citation]
PMID:
24633401
See all PubMed Citations (5)

Details of each submission

From Gharavi Laboratory,Columbia University, SCV000809402.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearch PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV001399187.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change replaces glycine with arginine at codon 452 of the COL4A3 protein (p.Gly452Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed in individual(s) with clinical features of Alport Syndrome (PMID: 24633401, 24854265, 24033287). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID:551440). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: May 10, 2021

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