ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.9866G>T (p.Ser3289Ile) (rs148932323)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000153703 SCV000203261 benign not specified 2016-04-06 criteria provided, single submitter clinical testing
Counsyl RCV000169100 SCV000220290 likely benign Autosomal recessive polycystic kidney disease 2014-05-01 criteria provided, single submitter literature only
Invitae RCV000169100 SCV000255211 benign Autosomal recessive polycystic kidney disease 2019-12-31 criteria provided, single submitter clinical testing
GeneDx RCV000489179 SCV000577808 likely pathogenic not provided 2015-04-30 criteria provided, single submitter clinical testing The S3289I variant in the PKHD1 gene has been reported previously in association with ARPKD (Sharp et al., 2005) though description of the patient's clinical features was not included. Although not present in the homozygous state, the NHLBI Exome Sequencing Project reports S3289I was observed in 0.43% (37/8600) of alleles from individuals of European ancestry, indicating it may be a rare variant in this population. The S3289I variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved across mammalian species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. A missense variant in a nearby residue (D3293V) has been reported in association with polycystic kidney disease (Bergmann et al., 2003), supporting the functional importance of this region of the protein. The S3289I variant is a strong candidate for a disease-causing variant, however the possibility it may be a rare benign variant cannot be excluded
Genetic Services Laboratory, University of Chicago RCV000153703 SCV000596429 likely benign not specified 2016-08-23 criteria provided, single submitter clinical testing
Mendelics RCV000169100 SCV001137137 benign Autosomal recessive polycystic kidney disease 2019-05-28 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000489179 SCV001154766 uncertain significance not provided 2016-09-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000169100 SCV001323267 uncertain significance Autosomal recessive polycystic kidney disease 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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