ClinVar Miner

Submissions for variant NM_001110556.2(FLNA):c.5255T>C (p.Leu1752Pro)

gnomAD frequency: 0.00001  dbSNP: rs1363194253
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV000762687 SCV000893022 uncertain significance not provided 2023-03-01 criteria provided, single submitter clinical testing FLNA: PM2, PP2
Invitae RCV001201534 SCV001372609 uncertain significance Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia 2024-01-29 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1744 of the FLNA protein (p.Leu1744Pro). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FLNA-related conditions. ClinVar contains an entry for this variant (Variation ID: 624458). 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 FLNA 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.
GeneDx RCV000762687 SCV001998551 uncertain significance not provided 2022-09-14 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function
Institute of Human Genetics, University Hospital Muenster RCV002287443 SCV002577990 uncertain significance Stroke disorder 2022-05-31 criteria provided, single submitter clinical testing ACMG categories: PM2
PreventionGenetics, part of Exact Sciences RCV003908076 SCV004727675 uncertain significance FLNA-related condition 2023-12-17 criteria provided, single submitter clinical testing The FLNA c.5255T>C variant is predicted to result in the amino acid substitution p.Leu1752Pro. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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