ClinVar Miner

Submissions for variant NM_004525.3(LRP2):c.13306G>A (p.Val4436Ile)

gnomAD frequency: 0.00004  dbSNP: rs750736741
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001967724 SCV002225607 uncertain significance not provided 2022-04-10 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 4436 of the LRP2 protein (p.Val4436Ile). This variant is present in population databases (rs750736741, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with LRP2-related conditions. 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. 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 RCV001967724 SCV002756511 uncertain significance not provided 2022-05-17 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics RCV002484710 SCV002788190 uncertain significance Donnai-Barrow syndrome 2022-05-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV004988971 SCV005612749 likely benign Inborn genetic diseases 2024-11-13 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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