ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.8206T>G (p.Trp2736Gly) (rs764880309)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000588557 SCV000699881 uncertain significance not provided 2017-03-27 criteria provided, single submitter clinical testing Variant summary: The PKHD1 c.8206T>G (p.Trp2736Gly) variant involves the alteration of a conserved nucleotide, is predicted to be damaging by 3/4 in silico tools and is located at an invariant site in fibrocystin/polyductin orthologs (Freedman_2013). ESE finder predicts that this variant creates a new binding site for SRp40. These predictions have yet to be confirmed by functional studies. This variant was found in 2/121184 control chromosomes from ExAC at a frequency of 0.0000165, which does not exceed the estimated maximal expected allele frequency of a pathogenic PKHD1 variant (0.0070711). This variant has been reported in three unrelated patients with autosomal recessive polycystic kidney disease in compound heterozygous state with other pathogenic/likely pathogenic variants (Sharp_2005, Denamur_2010, and Freedman_2013), the most recent publication classifying it as highly likely pathogenic. No other clinical testing laboratories have classified this variant in ClinVar, and well-established functional studies supporting a damaging effect on protein function have not yet been reported. Taken together, in the absence of additional strong evidence supporting a Pathogenic/Likely Pathogenic outcome, this variant is currently classified as VUS-possibly pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000765885 SCV000897291 uncertain significance Autosomal recessive polycystic kidney disease 2018-10-31 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000588557 SCV001246962 likely pathogenic not provided 2020-03-01 criteria provided, single submitter clinical testing

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