ClinVar Miner

Submissions for variant NM_015102.5(NPHP4):c.2006C>T (p.Thr669Ile)

gnomAD frequency: 0.00002  dbSNP: rs368327650
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002026638 SCV002316850 uncertain significance Nephronophthisis 2023-07-17 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 669 of the NPHP4 protein (p.Thr669Ile). This variant is present in population databases (rs368327650, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with NPHP4-related conditions. ClinVar contains an entry for this variant (Variation ID: 1516494). 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 NPHP4 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
Fulgent Genetics, Fulgent Genetics RCV002486730 SCV002782299 uncertain significance Nephronophthisis 4; Senior-Loken syndrome 4 2022-01-08 criteria provided, single submitter clinical testing

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