ClinVar Miner

Submissions for variant NM_015102.5(NPHP4):c.2020C>T (p.Arg674Cys)

gnomAD frequency: 0.00003  dbSNP: rs748042945
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001038987 SCV001202492 uncertain significance Nephronophthisis 2023-11-06 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 674 of the NPHP4 protein (p.Arg674Cys). This variant is present in population databases (rs748042945, gnomAD 0.04%). 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: 837610). 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 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.
Ambry Genetics RCV003363057 SCV004073407 uncertain significance Inborn genetic diseases 2023-07-12 criteria provided, single submitter clinical testing The c.2020C>T (p.R674C) alteration is located in exon 16 (coding exon 15) of the NPHP4 gene. This alteration results from a C to T substitution at nucleotide position 2020, causing the arginine (R) at amino acid position 674 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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