ClinVar Miner

Submissions for variant NM_002335.4(LRP5):c.3107G>A (p.Arg1036Gln) (rs61889560)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000174732 SCV000226093 likely benign not specified 2017-11-16 criteria provided, single submitter clinical testing
GeneDx RCV000767146 SCV000589340 uncertain significance not provided 2018-09-24 criteria provided, single submitter clinical testing The R1036Q variant in the LRP5 gene has been reported previously in association with osteoporosis, in individuals with autosomal dominant osteroporosis, and in affected individuals who were compound heterozygous for R1036Q and another missense variant; however this variant was also seen in cis with another missense variant (Q89R) and in family members without a diagnosis of osteoporosis or any fractures (Hartikka et al., 2005; Saarinen et al., 2010; Bardai et al., 2017). One in vitro functional study concluded this variant results in reduced Wnt signaling activity, however some measures of this reduced activity were not statistically significant (Korvala et al., 2012). The R1036Q variant is observed in 229/66720 (0.34%) alleles from individuals of Non-Finnish European background, in the ExAC dataset (Lek et al., 2016). The R1036Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is not conserved. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret R1036Q as a variant of uncertain significance.
Fulgent Genetics,Fulgent Genetics RCV000765011 SCV000896195 uncertain significance Bone mineral density quantitative trait locus 1; Exudative vitreoretinopathy 4; Exudative vitreoretinopathy 1; Worth disease; Postmenopausal osteoporosis; Autosomal dominant osteopetrosis 1; Van Buchem disease type 2; Osteoporosis with pseudoglioma; Polycystic liver disease 4 with or without kidney cysts 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000767146 SCV001107121 likely benign not provided 2020-11-22 criteria provided, single submitter clinical testing
Genetics Department,Polish Mother's Memorial Hospital Research Institute RCV001260288 SCV001244841 uncertain significance Autosomal dominant osteopetrosis 1 2020-04-06 criteria provided, single submitter research
Laboratory of Gastroenterology and Hepatology,Radboud University Medical Center RCV000162089 SCV000212088 not provided Polycystic kidney disease, adult type no assertion provided not provided

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