ClinVar Miner

Submissions for variant NM_000168.6(GLI3):c.2520G>A (p.Met840Ile)

gnomAD frequency: 0.00001  dbSNP: rs1283743237
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001878035 SCV002157872 uncertain significance Greig cephalopolysyndactyly syndrome; Pallister-Hall syndrome 2023-03-17 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 840 of the GLI3 protein (p.Met840Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GLI3-related conditions. ClinVar contains an entry for this variant (Variation ID: 1388744). 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 GLI3 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.
Fulgent Genetics, Fulgent Genetics RCV002490131 SCV002789386 uncertain significance Greig cephalopolysyndactyly syndrome; Pallister-Hall syndrome; Polysyndactyly 4; Polydactyly, postaxial, type A1 2024-04-23 criteria provided, single submitter clinical testing
Ambry Genetics RCV004975782 SCV005596406 uncertain significance Inborn genetic diseases 2024-07-25 criteria provided, single submitter clinical testing The c.2520G>A (p.M840I) alteration is located in exon 15 (coding exon 14) of the GLI3 gene. This alteration results from a G to A substitution at nucleotide position 2520, causing the methionine (M) at amino acid position 840 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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