Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001303591 | SCV001492840 | uncertain significance | Developmental and epileptic encephalopathy, 14; Autosomal dominant nocturnal frontal lobe epilepsy 5 | 2020-11-18 | 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 missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with KCNT1-related conditions. This variant is present in population databases (rs771326200, ExAC 0.002%). This sequence change replaces glutamic acid with aspartic acid at codon 1044 of the KCNT1 protein (p.Glu1044Asp). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. |
Neuberg Supratech Reference Laboratories Pvt Ltd, |
RCV003388607 | SCV004100416 | uncertain significance | Developmental and epileptic encephalopathy, 14 | criteria provided, single submitter | clinical testing | The missense variant p.E1044D in KCNT1 (NM_020822.3) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. It has been submitted to ClinVar as Uncertain Significance. The missense variant c.3132G>C (p.E1044D) in KCNT1 (NM_020822.3) is observed in 1/34548 (0.0029%) alleles from individuals of Latino background in the gnomAD dataset (Exome Aggregation Consortium et al., 2016), but was not seen in the homozygous state. In silico tools predict a contradictory effect (SIFT-damaging, Polyphen-2- Tolerated) and the residue is weakly conserved across species. For these reasons, this variant has been classified as Uncertain Significance. |