ClinVar Miner

Submissions for variant NM_000091.5(COL4A3):c.4700T>G (p.Ile1567Ser)

gnomAD frequency: 0.00003  dbSNP: rs371452712
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001139018 SCV001299124 uncertain significance Alport syndrome 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Cavalleri Lab, Royal College of Surgeons in Ireland RCV001171342 SCV001328289 uncertain significance Chronic kidney disease 2020-05-28 criteria provided, single submitter research PP3
GeneDx RCV001732015 SCV001982178 uncertain significance not provided 2023-04-12 criteria provided, single submitter clinical testing Identified in a patient with familial hematuria in published literature (Yu et al., 2019); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27391953, 32723786, Yu2019[abstract])
Fulgent Genetics, Fulgent Genetics RCV002489531 SCV002787139 uncertain significance Autosomal dominant Alport syndrome; Autosomal recessive Alport syndrome; Benign familial hematuria 2022-04-17 criteria provided, single submitter clinical testing
Invitae RCV001732015 SCV003279672 uncertain significance not provided 2024-01-25 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1567 of the COL4A3 protein (p.Ile1567Ser). This variant is present in population databases (rs371452712, gnomAD 0.05%). This missense change has been observed in individual(s) with chronic kidney disease (PMID: 32723786). ClinVar contains an entry for this variant (Variation ID: 829912). 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 COL4A3 protein function with a positive predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV003346253 SCV004059904 uncertain significance Inborn genetic diseases 2023-08-18 criteria provided, single submitter clinical testing The c.4700T>G (p.I1567S) alteration is located in exon 50 (coding exon 50) of the COL4A3 gene. This alteration results from a T to G substitution at nucleotide position 4700, causing the isoleucine (I) at amino acid position 1567 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV003906150 SCV004720953 uncertain significance COL4A3-related condition 2024-01-26 criteria provided, single submitter clinical testing The COL4A3 c.4700T>G variant is predicted to result in the amino acid substitution p.Ile1567Ser. This variant was reported as a variant of uncertain significance in an individual with arteriosclerosis (Table 1, Benson et al. 2020. PubMed ID: 32723786). This variant is reported in 0.056% of alleles in individuals of East Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Bioscientia Institut fuer Medizinische Diagnostik GmbH, Sonic Healthcare RCV001029860 SCV001192646 uncertain significance Autosomal dominant Alport syndrome 2019-10-23 no assertion criteria provided clinical testing

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