ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.930del (p.Thr311fs)

dbSNP: rs398124501
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000790780 SCV000225937 pathogenic not provided 2014-05-14 criteria provided, single submitter clinical testing
Invitae RCV000174614 SCV000260958 pathogenic Autosomal recessive polycystic kidney disease 2023-11-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Thr311Leufs*8) in the PKHD1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PKHD1 are known to be pathogenic (PMID: 19940839). This variant is present in population databases (rs398124501, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with congenital anomalies (PMID: 26633542). ClinVar contains an entry for this variant (Variation ID: 96442). 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.
Baylor Genetics RCV000174614 SCV001163074 pathogenic Autosomal recessive polycystic kidney disease criteria provided, single submitter clinical testing
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV000174614 SCV001427118 pathogenic Autosomal recessive polycystic kidney disease 2018-05-21 criteria provided, single submitter clinical testing A heterozygous frameshift deletion variant, NM_138694.3(PKHD1):c.930delC, has been identified in exon 13 of 67 of the PKHD1 gene. This deletion is predicted to create a frameshift starting at amino acid position 311, introducing a stop codon 8 residues downstream (NP_619639.3(PKHD1):p.(Thr311Leufs*8)). This variant is predicted to result in loss of protein function either through truncation (including the loss of multiple domains) or nonsense-mediated decay, which is a reported mechanism of pathogenicity for this gene. The variant is present in the gnomAD database at a frequency of 0.002% (7/275288 heterozygotes and 0 homozygotes). The variant has been previously reported as pathogenic in association with polycystic kidney disease (ClinVar). Based on the information available at the time of curation, this variant has been classified as PATHOGENIC.
Fulgent Genetics, Fulgent Genetics RCV001535976 SCV001752640 pathogenic Polycystic kidney disease 4 2021-06-30 criteria provided, single submitter clinical testing
GeneDx RCV000790780 SCV001778647 pathogenic not provided 2023-10-25 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 26633542, 30650191, 32939031)
Baylor Genetics RCV001535976 SCV004202205 pathogenic Polycystic kidney disease 4 2023-10-30 criteria provided, single submitter clinical testing
Counsyl RCV000174614 SCV001132268 likely pathogenic Autosomal recessive polycystic kidney disease 2015-07-08 no assertion criteria provided clinical testing

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