ClinVar Miner

Submissions for variant NM_002335.4(LRP5):c.4142C>T (p.Pro1381Leu)

gnomAD frequency: 0.00004  dbSNP: rs369637767
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001248036 SCV001421496 uncertain significance not provided 2024-09-05 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 1381 of the LRP5 protein (p.Pro1381Leu). This variant is present in population databases (rs369637767, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with LRP5-related conditions. ClinVar contains an entry for this variant (Variation ID: 972088). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt LRP5 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 RCV001248036 SCV001985603 uncertain significance not provided 2023-07-13 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics RCV005005122 SCV002786684 uncertain significance Bone mineral density quantitative trait locus 1; Exudative vitreoretinopathy 4; Worth disease; Autosomal dominant osteopetrosis 1; Osteoporosis with pseudoglioma; Polycystic liver disease 4 with or without kidney cysts 2024-04-16 criteria provided, single submitter clinical testing
Ambry Genetics RCV004034915 SCV004899358 uncertain significance Inborn genetic diseases 2023-12-20 criteria provided, single submitter clinical testing The c.4142C>T (p.P1381L) alteration is located in exon 20 (coding exon 20) of the LRP5 gene. This alteration results from a C to T substitution at nucleotide position 4142, causing the proline (P) at amino acid position 1381 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV004743364 SCV005353272 uncertain significance LRP5-related disorder 2024-09-19 no assertion criteria provided clinical testing The LRP5 c.4142C>T variant is predicted to result in the amino acid substitution p.Pro1381Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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