ClinVar Miner

Submissions for variant NM_004924.6(ACTN4):c.1279G>A (p.Ala427Thr)

gnomAD frequency: 0.00029  dbSNP: rs201128110
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, University of Leipzig Medical Center RCV000735721 SCV001428606 uncertain significance Focal segmental glomerulosclerosis 1 2017-03-29 criteria provided, single submitter clinical testing
GeneDx RCV002225721 SCV002504439 likely benign not provided 2021-02-16 criteria provided, single submitter clinical testing See Variant Classification Assertion Criteria.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002294377 SCV002587237 uncertain significance Focal segmental glomerulosclerosis 2022-07-07 criteria provided, single submitter clinical testing
Invitae RCV002225721 SCV003288192 uncertain significance not provided 2024-01-15 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 427 of the ACTN4 protein (p.Ala427Thr). This variant is present in population databases (rs201128110, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with focal segmental glomerulosclerosis (PMID: 16251236, 23890478, 29869118, 31027891). ClinVar contains an entry for this variant (Variation ID: 599123). 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 not expected to disrupt ACTN4 protein function with a negative predictive value of 80%. 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.
CeGaT Center for Human Genetics Tuebingen RCV002225721 SCV004141655 likely benign not provided 2023-01-01 criteria provided, single submitter clinical testing ACTN4: BP4, BS2
Bioscientia Institut fuer Medizinische Diagnostik GmbH, Sonic Healthcare RCV000735721 SCV000863874 uncertain significance Focal segmental glomerulosclerosis 1 2018-05-17 no assertion criteria provided clinical testing

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