ClinVar Miner

Submissions for variant NM_153240.5(NPHP3):c.3809T>C (p.Leu1270Pro) (rs794727430)

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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 RCV000176698 SCV000228395 uncertain significance not provided 2014-11-17 criteria provided, single submitter clinical testing
Invitae RCV000475008 SCV000552112 uncertain significance Nephronophthisis 2016-10-10 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 1270 of the NPHP3 protein (p.Leu1270Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a NPHP3-related disease. ClinVar contains an entry for this variant (Variation ID: 195995). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with features of a NPHP3-related disease. This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. 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. In summary, this variant is a rare missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

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