ClinVar Miner

Submissions for variant NM_001110556.2(FLNA):c.3308C>T (p.Thr1103Met)

gnomAD frequency: 0.00001  dbSNP: rs781970327
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000196871 SCV000250382 uncertain significance not provided 2015-06-02 criteria provided, single submitter clinical testing p.Thr1103Met (ACG>ATG): c.3308 C>T in exon 22 in the FLNA Gene (NM_001456.3). The T1103M variant in the FLNA gene has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The T1103M variant was not observed in approximately 6100 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common variant in these populations. The T1103M variant is a non-conservative amino acid substitution, which occurs within Filamin 9 repeat at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret T1103M as a variant of unknown significance. This variant was found in HG19-EXOME-
Labcorp Genetics (formerly Invitae), Labcorp RCV001046907 SCV001210828 uncertain significance Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia 2022-01-15 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 213469). This variant has not been reported in the literature in individuals affected with FLNA-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 1103 of the FLNA protein (p.Thr1103Met).

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