ClinVar Miner

Submissions for variant NM_017415.3(KLHL3):c.1670A>G (p.Tyr557Cys)

gnomAD frequency: 0.00001  dbSNP: rs199469645
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV003556076 SCV004292857 uncertain significance not provided 2023-12-15 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 557 of the KLHL3 protein (p.Tyr557Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with pseudohypoaldosteronism type II (PMID: 22266938). ClinVar contains an entry for this variant (Variation ID: 30521). 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 KLHL3 protein function with a positive 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.
OMIM RCV000023478 SCV000044769 pathogenic Pseudohypoaldosteronism type 2D 2012-01-22 no assertion criteria provided literature only
Richard Lifton Laboratory, Yale University School of Medicine RCV000128524 SCV000119174 pathogenic Pseudohypoaldosteronism type 2A no assertion criteria provided not provided Converted during submission to Pathogenic.

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