Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000557459 | SCV000630819 | uncertain significance | Walker-Warburg congenital muscular dystrophy | 2022-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 98 of the FKTN protein (p.Thr98Ser). 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 variant has not been reported in the literature in individuals affected with FKTN-related conditions. ClinVar contains an entry for this variant (Variation ID: 459221). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
Ambry Genetics | RCV002438328 | SCV002747821 | uncertain significance | Cardiovascular phenotype | 2022-11-15 | criteria provided, single submitter | clinical testing | The p.T98S variant (also known as c.293C>G), located in coding exon 3 of the FKTN gene, results from a C to G substitution at nucleotide position 293. The threonine at codon 98 is replaced by serine, an amino acid with similar properties. This amino acid position is poorly 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. |
Revvity Omics, |
RCV003144321 | SCV003832679 | uncertain significance | not provided | 2021-01-06 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003915501 | SCV004727881 | uncertain significance | FKTN-related condition | 2023-10-31 | criteria provided, single submitter | clinical testing | The FKTN c.293C>G variant is predicted to result in the amino acid substitution p.Thr98Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.024% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/9-108363553-C-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Natera, |
RCV000557459 | SCV002078756 | uncertain significance | Walker-Warburg congenital muscular dystrophy | 2019-10-28 | no assertion criteria provided | clinical testing |