ClinVar Miner

Submissions for variant NM_004525.3(LRP2):c.13936G>A (p.Ala4646Thr)

gnomAD frequency: 0.00001  dbSNP: rs202210831
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001752430 SCV001997278 uncertain significance not provided 2019-12-20 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics RCV002489785 SCV002803825 uncertain significance Donnai-Barrow syndrome 2022-04-29 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001752430 SCV003022003 uncertain significance not provided 2022-08-21 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 4646 of the LRP2 protein (p.Ala4646Thr). This variant is present in population databases (rs202210831, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with LRP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1311447). 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 LRP2 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.
Ambry Genetics RCV002540428 SCV003609617 uncertain significance Inborn genetic diseases 2022-02-10 criteria provided, single submitter clinical testing The c.13936G>A (p.A4646T) alteration is located in exon 79 (coding exon 79) of the LRP2 gene. This alteration results from a G to A substitution at nucleotide position 13936, causing the alanine (A) at amino acid position 4646 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.