Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000635557 | SCV000756974 | uncertain significance | Birt-Hogg-Dube syndrome | 2022-05-24 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 529996). This missense change has been observed in individual(s) with Birt–Hogg–Dube´ syndrome (PMID: 27258496). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 549 of the FLCN protein (p.Leu549Val). |
Ambry Genetics | RCV002388037 | SCV002703419 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-05 | criteria provided, single submitter | clinical testing | The p.L549V variant (also known as c.1645C>G), located in coding exon 11 of the FLCN gene, results from a C to G substitution at nucleotide position 1645. The leucine at codon 549 is replaced by valine, an amino acid with highly similar properties. This alteration was identified in an individual diagnosed with renal cell cancer at 49, papillary thyroid cancer and undefined skin lesions (Dong L et al. Medicine (Baltimore), 2016 May;95:e3695). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |