Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000791573 | SCV000930830 | pathogenic | Nephronophthisis | 2023-12-09 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Lys185Asnfs*7) in the NPHP1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NPHP1 are known to be pathogenic (PMID: 23559409). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with Joubert syndrome (PMID: 26477546). ClinVar contains an entry for this variant (Variation ID: 638899). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Johns Hopkins Genomics, |
RCV001260993 | SCV001438373 | pathogenic | Joubert syndrome with renal defect | 2020-09-24 | criteria provided, single submitter | clinical testing | This variant has been reported in an individual with Joubert syndrome. This frameshift variant results in a premature stop codon, likely leading to nonsense-mediated decay and lack of protein production. This NPHP1 variant (rs577698811) is rare (<0.1%) in a large population dataset (gnomAD: 9/282044 total alleles; 0.003%; no homozygotes), and has been reported in ClinVar. We consider this variant to be pathogenic. |
Baylor Genetics | RCV001260993 | SCV004191323 | pathogenic | Joubert syndrome with renal defect | 2023-09-17 | criteria provided, single submitter | clinical testing |