Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000182195 | SCV000234498 | likely pathogenic | not provided | 2013-10-25 | criteria provided, single submitter | clinical testing | p.Lys515Asn (AAG>AAT): c.1545 G>T in exon 12 of the KCNQ1 gene (NM_000218.2). The Lys515Asn variant in the KCNQ1 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Lys515Asn results in a semi-conservative amino acid substitution of a positively charged Lysine residue with a neutral, polar Asparagine residue at a position that is conserved across species. In silico analysis predicts Lys515Asn is probably damaging to the protein structure/function. Mutations in nearby residues (Ile514Thr, Ile517Thr) have been reported in association with LQTS, further supporting the functional importance of this region of the protein. Furthermore, the Lys515Asn variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. In summary, while Lys515Asn is a good candidate for a disease-causing mutation, with the clinical and molecular information available at this time we cannot unequivocally determine the clinical significance of this variant. The variant is found in LQT panel(s). |
Labcorp Genetics |
RCV001852306 | SCV002255515 | uncertain significance | Long QT syndrome | 2020-11-25 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with KCNQ1-related conditions. ClinVar contains an entry for this variant (Variation ID: 200852). This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with asparagine at codon 515 of the KCNQ1 protein (p.Lys515Asn). The lysine residue is moderately conserved and there is a moderate physicochemical difference between lysine and asparagine. |