ClinVar Miner

Submissions for variant NM_033380.3(COL4A5):c.1643G>A (p.Gly548Asp)

dbSNP: rs281874673
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001228281 SCV001400675 pathogenic not provided 2023-06-24 criteria provided, single submitter clinical testing 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. ClinVar contains an entry for this variant (Variation ID: 24432). This missense change has been observed in individuals with Alport syndrome (PMID: 19919694, 20378821). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 548 of the COL4A5 protein (p.Gly548Asp). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site.
Molecular Biology Laboratory, Fundació Puigvert RCV000021311 SCV001425040 likely pathogenic X-linked Alport syndrome 2020-02-01 criteria provided, single submitter research
Sydney Genome Diagnostics, Children's Hospital Westmead RCV001328298 SCV001449283 pathogenic Alport syndrome 2018-09-06 no assertion criteria provided clinical testing This patient is heterozygous for a known pathogenic variant, c.1643G>A (p.Gly548Asp), in exon 24 of the COL4A5 gene. This variant results in the substitution of one of the invariant glycine residues in the triple helical domain of type IV collagen and is considered to be pathogenic. This variant has also been previously reported in the COL4A5 database with an age of onset greater than 30 years of age (see http://www.arup.utah.edu/database/ALPORT/ALPORT_display.php).

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