ClinVar Miner

Submissions for variant NM_002335.4(LRP5):c.407A>C (p.Asn136Thr)

gnomAD frequency: 0.00003  dbSNP: rs759063931
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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) RCV000594637 SCV000703898 uncertain significance not provided 2016-12-27 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000594637 SCV001381722 uncertain significance not provided 2024-01-24 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with threonine, which is neutral and polar, at codon 136 of the LRP5 protein (p.Asn136Thr). This variant is present in population databases (rs759063931, gnomAD 0.004%). 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: 498738). 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 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 RCV002491193 SCV002781455 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 2021-08-24 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003409860 SCV004107360 uncertain significance LRP5-related disorder 2023-05-11 criteria provided, single submitter clinical testing The LRP5 c.407A>C variant is predicted to result in the amino acid substitution p.Asn136Thr. This variant is reported in 0.0047% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/11-68115630-A-C). A different variant affecting the same amino acid (p.Asn136Lys) was reported in an individual with osteoporosis (Table 2, Caetano da Silva. 2021. PubMed ID: 33939331). 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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