Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001244610 | SCV001417840 | likely pathogenic | Long QT syndrome | 2024-10-30 | criteria provided, single submitter | clinical testing | This variant, c.172_177delinsCCCCCT, is a complex sequence change that results in the deletion of 2 and insertion of 2 amino acid(s) in the KCNE1 protein (p.Thr58_Leu59delinsProPro). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This variant has been observed in individuals with Jervell and Lange-Nielsen syndrome and/or long QT syndrome (PMID: 9328483, 10973849, 31941373; internal data). It has also been observed to segregate with disease in related individuals. This variant is also known as T59P/L60P. ClinVar contains an entry for this variant (Variation ID: 132658). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt KCNE1 protein function with a positive predictive value of 95%. Experimental studies have shown that this variant affects KCNE1 function (PMID: 11530100, 19907016). 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. |
| Gene |
RCV001588813 | SCV001822422 | likely pathogenic | not provided | 2024-06-06 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (gnomAD); Published functional studies demonstrate that the p.(T58P)/p.(L59P) variant severely weakens the interaction of KCNE1 with KCNQ1 and leads to an inability to modulate channel gating and the production of currents that lack the slow activation profile (PMID: 19907016); In silico analysis supports a deleterious effect on protein structure/function; Also known as p.(T59P)/p.(L60P) or p.(T58P)/p.(L59P) (PMID: 9328483, 11530100, 19907016); This variant is associated with the following publications: (PMID: 11530100, 11692163, 26410412, 9328483, 31941373, 19907016, 10973849) |
| Fulgent Genetics, |
RCV002476967 | SCV002787877 | likely pathogenic | Jervell and Lange-Nielsen syndrome 2; Long QT syndrome 5 | 2021-10-21 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000014417 | SCV000034666 | pathogenic | Jervell and Lange-Nielsen syndrome 2 | 1997-11-01 | no assertion criteria provided | literature only |