ClinVar Miner

Submissions for variant NM_002334.4(LRP4):c.3752C>T (p.Pro1251Leu)

gnomAD frequency: 0.00020  dbSNP: rs145422541
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000402952 SCV000372167 uncertain significance Cenani-Lenz syndactyly syndrome 2016-06-14 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001859808 SCV002272060 uncertain significance Cenani-Lenz syndactyly syndrome; Sclerosteosis 2; Congenital myasthenic syndrome 17 2022-06-10 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 1251 of the LRP4 protein (p.Pro1251Leu). This variant is present in population databases (rs145422541, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with LRP4-related conditions. ClinVar contains an entry for this variant (Variation ID: 304866). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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 RCV001859808 SCV002786096 uncertain significance Cenani-Lenz syndactyly syndrome; Sclerosteosis 2; Congenital myasthenic syndrome 17 2024-04-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV002520722 SCV003630459 uncertain significance Inborn genetic diseases 2022-12-06 criteria provided, single submitter clinical testing The c.3752C>T (p.P1251L) alteration is located in exon 27 (coding exon 27) of the LRP4 gene. This alteration results from a C to T substitution at nucleotide position 3752, causing the proline (P) at amino acid position 1251 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 RCV004537715 SCV004119561 uncertain significance LRP4-related disorder 2023-04-19 criteria provided, single submitter clinical testing The LRP4 c.3752C>T variant is predicted to result in the amino acid substitution p.Pro1251Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.025% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/11-46897180-G-A). 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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