ClinVar Miner

Submissions for variant NM_023067.4(FOXL2):c.195G>A (p.Met65Ile)

gnomAD frequency: 0.00001  dbSNP: rs1057516145
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia RCV000408759 SCV000484849 likely pathogenic Blepharophimosis, ptosis, and epicanthus inversus syndrome 2016-11-03 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003678999 SCV004412262 likely pathogenic not provided 2023-04-24 criteria provided, single submitter clinical testing This missense change has been observed in individual(s) with clinical features of blepharophimosis, ptosis, and epicanthus inversus syndrome (Invitae). It has also been observed to segregate with disease in related individuals. This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 65 of the FOXL2 protein (p.Met65Ile). This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 369892). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant disrupts the p.Met65 amino acid residue in FOXL2. Other variant(s) that disrupt this residue have been observed in individuals with FOXL2-related conditions (PMID: 18642388; Invitae), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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