Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001851612 | SCV002286185 | likely pathogenic | Walker-Warburg congenital muscular dystrophy | 2024-02-05 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 114 of the FKTN protein (p.Ala114Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with FKTN-related conditions (PMID: 17878207, 19342235). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 3213). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on FKTN protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
OMIM | RCV000003368 | SCV000023526 | pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2M | 2009-05-01 | no assertion criteria provided | literature only | |
Counsyl | RCV000675045 | SCV000800477 | uncertain significance | Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 | 2017-01-09 | no assertion criteria provided | clinical testing | This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. |