ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.3747T>G (p.Cys1249Trp) (rs748540413)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000667920 SCV000792445 uncertain significance Autosomal recessive polycystic kidney disease 2017-06-28 criteria provided, single submitter clinical testing
Invitae RCV000667920 SCV000958909 pathogenic Autosomal recessive polycystic kidney disease 2018-12-06 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tryptophan at codon 1249 of the PKHD1 protein (p.Cys1249Trp). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tryptophan. This variant is present in population databases (rs748540413, ExAC 0.005%). This variant has been observed in several individuals affected with autosomal recessive polycystic kidney disease (PMID: 11919560, 19914852, 29956005, Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 552624). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). For these reasons, this variant has been classified as Pathogenic.

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