Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000694143 | SCV000822574 | uncertain significance | Birt-Hogg-Dube syndrome | 2023-08-05 | 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 572698). This variant has not been reported in the literature in individuals affected with FLCN-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change results in a frameshift in the FLCN gene (p.His564Thrfs*24). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 16 amino acid(s) of the FLCN protein and extend the protein by 7 additional amino acid residues. |
Ambry Genetics | RCV001012734 | SCV001173223 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-19 | criteria provided, single submitter | clinical testing | The c.1689delA variant, located in coding exon 11 of the FLCN gene, results from a deletion of one nucleotide at nucleotide position 1689, causing a translational frameshift with a predicted alternate stop codon (p.H564Tfs*24). Frameshifts are typically deleterious in nature, however, this frameshift occurs at the 3' terminus of FLCN, is not expected to trigger nonsense-mediated mRNA decay, impacts only the last 16 amino acids of the protein, and elongates the FLCN protein by 7 amino acids. The exact functional impact of these altered amino acids is unknown at this time. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |