ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.2191G>A (p.Val731Ile)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
All of Us Research Program, National Institutes of Health RCV004014380 SCV004842079 uncertain significance Hypercholesterolemia, familial, 1 2023-12-13 criteria provided, single submitter clinical testing This missense variant replaces valine with isoleucine at codon 731 of the LDLR protein. This variant is also known as p.Val710Ile in the mature protein. Computational prediction suggests that this variant may not impact protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with LDLR-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV005103347 SCV005830926 uncertain significance Familial hypercholesterolemia 2025-01-22 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 731 of the LDLR protein (p.Val731Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with LDLR-related conditions. ClinVar contains an entry for this variant (Variation ID: 3074846). 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) indicates that this missense variant is not expected to disrupt LDLR protein function with a negative predictive value of 95%. 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.

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