ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.694G>A (p.Ala232Thr)

gnomAD frequency: 0.00001  dbSNP: rs72658857
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001177671 SCV001341923 uncertain significance Familial hypercholesterolemia 2020-03-05 criteria provided, single submitter clinical testing This missense variant (also known as p.Ala211Thr in the mature protein) replaces alanine with threonine at codon 232 of the LDLR protein. Computational prediction tool suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold ≤0.5, PMID: 27666373). This variant changes the last nucleotide c.G of exon 4 and is predicted to impact RNA splicing by splice site prediction tools. However, c.G nucleotide at this position is poorly conserved and variant c.A nucleotide is tolerated in over 10 mammalian species, suggesting that the variant is likely tolerated for function. To our knowledge, functional studies have not been performed for this variant。 This variant been reported in an individual affected with familial hypercholesterolemia (PMID: 29269200). This variant has also been identified in 3/244710 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
All of Us Research Program, National Institutes of Health RCV004807324 SCV005426466 uncertain significance Hypercholesterolemia, familial, 1 2024-05-14 criteria provided, single submitter clinical testing This missense variant (also known as p.Ala211Thr in the mature protein) replaces alanine with threonine at codon 232 of the LDLR protein. Computational prediction tool suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <=0.5, PMID: 27666373). This variant changes the last nucleotide c.G of exon 4 and is predicted to impact RNA splicing by splice site prediction tools. However, c.G nucleotide at this position is poorly conserved and variant c.A nucleotide is tolerated in over 10 mammalian species, suggesting that the variant is likely tolerated for function. To our knowledge, functional studies have not been performed for this variant. This variant been reported in an individual affected with familial hypercholesterolemia (PMID: 29269200). This variant has also been identified in 3/244710 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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.