ClinVar Miner

Submissions for variant NM_004525.3(LRP2):c.10703C>T (p.Pro3568Leu)

gnomAD frequency: 0.00001  dbSNP: rs753477259
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000273127 SCV000332968 uncertain significance not provided 2015-07-27 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002503983 SCV002806914 uncertain significance Donnai-Barrow syndrome 2022-01-19 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000273127 SCV002943575 uncertain significance not provided 2024-01-25 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 3568 of the LRP2 protein (p.Pro3568Leu). This variant is present in population databases (rs753477259, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with LRP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 281919). 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 not expected to disrupt LRP2 protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV000273127 SCV005326746 uncertain significance not provided 2023-09-06 criteria provided, single submitter clinical testing Observed with a LRP2 variant on the same allele (in cis) as well as another LRP2 variant on the opposite allele (in trans) in siblings with myopia and low molecular weight proteinuria in the literature (Gritti et al., 2023); Observed in a patient with hypoplastic left heart syndrome in the literature, although additional clinical and familial segregation information was not available (Theis et al., 2020); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 37592754, 33006316)

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