ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.12110T>C (p.Leu4037Pro) (rs199900211)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000730606 SCV000858354 uncertain significance not provided 2018-06-14 criteria provided, single submitter clinical testing
Invitae RCV000198885 SCV000255209 uncertain significance Autosomal recessive polycystic kidney disease 2016-02-05 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 4037 of the PKHD1 protein (p.Leu4037Pro). The leucine residue is weakly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is present in population databases (rs199900211, ExAC 0.02%). This variant has been reported in a terminated fetus affected with an unknown lethal congenital anomaly, as well as its unaffected mother (PMID: 24128419). However, two pathogenic alleles were identified in the KIF14 gene, which suggests that this c.12110T>C substitution in PKHD1 was not the primary cause of disease in this fetus. ClinVar contains an entry for this variant (Variation ID: 216821). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this is a rare missense change with uncertain impact on protein function. Although there is no indication that this variant causes disease, the evidence is insufficient at this time to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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