ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.11740C>T (p.Arg3914Ter)

gnomAD frequency: 0.00001  dbSNP: rs761704401
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000670650 SCV000795532 uncertain significance Autosomal recessive polycystic kidney disease 2017-11-09 criteria provided, single submitter clinical testing
Invitae RCV000670650 SCV002932497 pathogenic Autosomal recessive polycystic kidney disease 2023-12-26 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg3914*) in the PKHD1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 161 amino acid(s) of the PKHD1 protein. This variant is present in population databases (rs761704401, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with PKHD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 554930). This variant disrupts a region of the PKHD1 protein in which other variant(s) (p.Arg3961*) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics, part of Exact Sciences RCV003392511 SCV004119546 pathogenic PKHD1-related disorder 2023-06-06 criteria provided, single submitter clinical testing The PKHD1 c.11740C>T variant is predicted to result in premature protein termination (p.Arg3914*). This variant was reported in a cohort of individuals being analyzed for carrier screening (Zhao et al 2019. PubMed ID: 30275481), but to our knowledge has not been reported in affected individuals with PKHD1-related phenotypes. This variant is reported in 0.016% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/6-51491840-G-A). Truncating variants in PKHD1 are expected to be pathogenic. This variant is interpreted as pathogenic.
Baylor Genetics RCV003459618 SCV004204561 likely pathogenic Polycystic kidney disease 4 2023-08-31 criteria provided, single submitter clinical testing

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