ClinVar Miner

Submissions for variant NM_002334.4(LRP4):c.2980G>A (p.Val994Ile)

gnomAD frequency: 0.00009  dbSNP: rs370091369
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000800789 SCV000940523 uncertain significance Cenani-Lenz syndactyly syndrome; Sclerosteosis 2; Congenital myasthenic syndrome 17 2024-01-25 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 994 of the LRP4 protein (p.Val994Ile). This variant is present in population databases (rs370091369, gnomAD 0.01%). 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: 646493). 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 expected to disrupt LRP4 protein function with a positive predictive value of 80%. 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 RCV000800789 SCV002788342 uncertain significance Cenani-Lenz syndactyly syndrome; Sclerosteosis 2; Congenital myasthenic syndrome 17 2024-02-07 criteria provided, single submitter clinical testing
Ambry Genetics RCV002534655 SCV003535780 uncertain significance Inborn genetic diseases 2022-02-10 criteria provided, single submitter clinical testing The c.2980G>A (p.V994I) alteration is located in exon 21 (coding exon 21) of the LRP4 gene. This alteration results from a G to A substitution at nucleotide position 2980, causing the valine (V) at amino acid position 994 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx RCV004723201 SCV005333525 uncertain significance not provided 2023-08-02 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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