Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000724028 | SCV000700705 | pathogenic | not provided | 2017-06-15 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001036532 | SCV001199900 | pathogenic | Walker-Warburg congenital muscular dystrophy | 2024-01-06 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 307 of the FKTN protein (p.Arg307Gln). This variant is present in population databases (rs119463992, gnomAD 0.01%). This missense change has been observed in individual(s) with FKTN-related conditions (PMID: 17044012, 19179078, 19396839, 25821721, 30060766). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 3208). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt FKTN protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects FKTN function (PMID: 26923585). For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001192872 | SCV001361296 | pathogenic | Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 | 2019-05-02 | criteria provided, single submitter | clinical testing | Variant summary: FKTN c.920G>A (p.Arg307Gln) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 249118 control chromosomes (gnomAD). c.920G>A has been reported in the literature in multiple affected individuals (Ceyhan-Birsoy_2015, Godfrey_2007, Johnson_2018, Yis_2011). These data indicate that the variant is very likely to be associated with disease. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Baylor Genetics | RCV003466793 | SCV004199742 | pathogenic | Dilated cardiomyopathy 1X | 2023-05-05 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000003362 | SCV000023520 | pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2M | 2009-05-26 | no assertion criteria provided | literature only | |
| OMIM | RCV001254647 | SCV001430679 | pathogenic | Muscular dystrophy-dystroglycanopathy (congenital without intellectual disability), type B4 | 2009-05-26 | no assertion criteria provided | literature only |