ClinVar Miner

Submissions for variant NM_002335.4(LRP5):c.680C>T (p.Ser227Leu)

gnomAD frequency: 0.00005  dbSNP: rs200384949
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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 RCV001053617 SCV001217889 uncertain significance not provided 2025-01-20 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 227 of the LRP5 protein (p.Ser227Leu). This variant is present in population databases (rs200384949, 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: 849611). 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) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on LRP5 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.
Fulgent Genetics, Fulgent Genetics RCV002489632 SCV002782389 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 2022-04-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV002553325 SCV003747744 uncertain significance Inborn genetic diseases 2021-11-15 criteria provided, single submitter clinical testing The c.680C>T (p.S227L) alteration is located in exon 3 (coding exon 3) of the LRP5 gene. This alteration results from a C to T substitution at nucleotide position 680, causing the serine (S) at amino acid position 227 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 RCV004743268 SCV005363648 uncertain significance LRP5-related disorder 2024-08-30 no assertion criteria provided clinical testing The LRP5 c.680C>T variant is predicted to result in the amino acid substitution p.Ser227Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.014% of alleles in individuals of European (Non-Finnish) 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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