ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.5513A>G (p.Tyr1838Cys) (rs777999875)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000411938 SCV000485496 likely pathogenic Autosomal recessive polycystic kidney disease 2015-12-23 criteria provided, single submitter clinical testing
Invitae RCV000411938 SCV000754658 likely pathogenic Autosomal recessive polycystic kidney disease 2019-12-18 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 1838 of the PKHD1 protein (p.Tyr1838Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is present in population databases (rs777999875, ExAC 0.002%). This variant has been observed to be homozygous or in combination with another PKHD1 variant in several individuals affected with autosomal recessive polycystic kidney disease (PMID: 15698423, 29956005). ClinVar contains an entry for this variant (Variation ID: 370239). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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