ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.1968G>T (p.Trp656Cys)

dbSNP: rs1209068432
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001879271 SCV002142001 pathogenic Autosomal recessive polycystic kidney disease 2021-08-21 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This sequence change replaces tryptophan with cysteine at codon 656 of the PKHD1 protein (p.Trp656Cys). The tryptophan residue is highly conserved and there is a large physicochemical difference between tryptophan and cysteine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with polycystic kidney disease (PMID: 12506140). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PKHD1 protein function.

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