Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000865430 | SCV001006391 | likely benign | Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia | 2024-02-01 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001539581 | SCV001757369 | uncertain significance | not provided | 2021-04-27 | criteria provided, single submitter | clinical testing | Reported in ClinVar (ClinVar Variant ID# 698162; Landrum et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Apparently de novo variant in a female patient with lifelong thrombocytopenia, developmental delay, dysmorphic features and hypoplasia of the corpus callosum (Bastida et al., 2018); however, only genes associated with inherited platelet disorders were tested; This variant is associated with the following publications: (PMID: 28983057) |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003396504 | SCV004121857 | uncertain significance | not specified | 2023-10-19 | criteria provided, single submitter | clinical testing | Variant summary: FLNA c.3695C>T (p.Thr1232Ile) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.8e-05 in 180070 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.3695C>T has been reported in the literature as de novo in a female individual who underwent multigene panel testing for a suspected inherited platelet disorder (filaminopathy) and presented with lifelong thrombocytopenia with mildly increased platelet size, facial abnormalities and corpus callosum hypoplasia (Bastida_2018). This report does not provide unequivocal conclusions about association of the variant with Periventricular Nodular Heterotopia or other FLNA-associated disorders. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 28983057). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. One submitter classified the variant as likely benign, and one submitter classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |