ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.4292G>A (p.Cys1431Tyr) (rs753307105)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000328052 SCV000340904 uncertain significance not provided 2017-09-15 criteria provided, single submitter clinical testing
Invitae RCV000675159 SCV000948834 likely pathogenic Autosomal recessive polycystic kidney disease 2019-05-06 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tyrosine at codon 1431 of the PKHD1 protein (p.Cys1431Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant is present in population databases (rs753307105, ExAC 0.03%). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with polycystic kidney disease (PMID: 27225849). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. It has also been identified in individuals affected with polycystic kidney disease (Invitae). ClinVar contains an entry for this variant (Variation ID: 287201). 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"). 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.
Counsyl RCV000675159 SCV000800776 likely pathogenic Autosomal recessive polycystic kidney disease 2019-06-09 no assertion criteria provided clinical testing

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