ClinVar Miner

Submissions for variant NM_001128178.3(NPHP1):c.604G>C (p.Val202Leu)

gnomAD frequency: 0.00001  dbSNP: rs753605280
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001232297 SCV001404847 uncertain significance Nephronophthisis 2022-10-07 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 202 of the NPHP1 protein (p.Val202Leu). This variant is present in population databases (rs753605280, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with NPHP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 959022). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on NPHP1 protein function. 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 RCV002497793 SCV002784178 uncertain significance Joubert syndrome with renal defect; Nephronophthisis 1; Senior-Loken syndrome 1 2022-05-30 criteria provided, single submitter clinical testing
Ambry Genetics RCV003166421 SCV003882096 uncertain significance Inborn genetic diseases 2023-02-06 criteria provided, single submitter clinical testing The c.604G>C (p.V202L) alteration is located in exon 6 (coding exon 6) of the NPHP1 gene. This alteration results from a G to C substitution at nucleotide position 604, causing the valine (V) at amino acid position 202 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV004734061 SCV005346827 uncertain significance NPHP1-related disorder 2024-08-31 no assertion criteria provided clinical testing The NPHP1 c.604G>C variant is predicted to result in the amino acid substitution p.Val202Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.023% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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