Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000556971 | SCV000651019 | likely benign | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2024-01-19 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001731770 | SCV001982050 | uncertain significance | not provided | 2023-06-05 | 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 has a deleterious effect on protein structure/function |
Ambry Genetics | RCV002324031 | SCV002628352 | uncertain significance | Cardiovascular phenotype | 2023-12-14 | criteria provided, single submitter | clinical testing | The p.N1366S variant (also known as c.4097A>G), located in coding exon 23 of the FLNC gene, results from an A to G substitution at nucleotide position 4097. The asparagine at codon 1366 is replaced by serine, an amino acid with highly similar properties. This alteration has been reported in a pediatric cardiomyopathy cohort (Ware SM et al. Am J Hum Genet, 2022 Feb;109:282-298). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Victorian Clinical Genetics Services, |
RCV002470906 | SCV002766679 | uncertain significance | Primary dilated cardiomyopathy | 2021-05-06 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3B. Following criteria are met: 0103 - Loss of function and gain of function are known mechanisms of disease in this gene and are associated with FLNC-related disease. Loss of function variants have been reported to cause myofibrillar myopathy, 5 (MIM#609524), distal myopathy, 4 (MIM#614065), familial hypertrophic cardiomyopathy, 26 (MIM#617047) and dilated cardiomyopathy (PMID: 32112656). Gain of function variants have also been reported to cause distal myopathy, 4 (MIM#614065) (PMID: 28008423, PMID: 23109048). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from asparagine to serine. (I) 0251 - This variant is heterozygous. (I) 0302 - Variant is present in gnomAD (v2) <0.001 for a dominant condition (44 heterozygotes, 0 homozygotes). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0600 - Variant is located in the annotated filamin 12 repeat (NCBI, Uniprot). (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0809 - Previous evidence of pathogenicity for this variant is inconclusive. This variant has been previously reported as a VUS (ClinVar). (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
Revvity Omics, |
RCV001731770 | SCV003833092 | uncertain significance | not provided | 2022-09-14 | criteria provided, single submitter | clinical testing | |
Ce |
RCV001731770 | SCV004032768 | uncertain significance | not provided | 2023-09-01 | criteria provided, single submitter | clinical testing |