ClinVar Miner

Submissions for variant NM_002335.4(LRP5):c.4319C>T (p.Pro1440Leu)

gnomAD frequency: 0.00004  dbSNP: rs528693139
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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 RCV001954322 SCV002241811 uncertain significance not provided 2024-11-11 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 1440 of the LRP5 protein (p.Pro1440Leu). This variant is present in population databases (rs528693139, gnomAD 0.01%). 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: 1462668). 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.
Fulgent Genetics, Fulgent Genetics RCV002492148 SCV002775893 uncertain significance Bone mineral density quantitative trait locus 1; Exudative vitreoretinopathy 4; Exudative vitreoretinopathy 1; Worth disease; Autosomal dominant osteopetrosis 1; Osteoporosis with pseudoglioma; Osteoporosis; Polycystic liver disease 4 with or without kidney cysts 2021-07-15 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001954322 SCV004704151 uncertain significance not provided 2024-01-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV004988989 SCV005614478 uncertain significance Inborn genetic diseases 2024-10-01 criteria provided, single submitter clinical testing The c.4319C>T (p.P1440L) 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 4319, causing the proline (P) at amino acid position 1440 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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