Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001212412 | SCV001383995 | uncertain significance | Gastrointestinal stromal tumor | 2023-02-06 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 909 of the KIT protein (p.Ala909Leu). 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 not been reported in the literature in individuals affected with KIT-related conditions. ClinVar contains an entry for this variant (Variation ID: 942424). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant  is likely to be tolerated. 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. |
| Ambry Genetics | RCV002429901 | SCV002741553 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-03-25 | criteria provided, single submitter | clinical testing | The c.2725_2726delGCinsTT variant (also known as p.A909L), located in coding exon 20 of the KIT gene, results from an in-frame deletion of GC and insertion of TT at nucleotide positions 2725 to 2726. This results in the substitution of the alanine residue for a leucine residue at codon 909. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be neutral by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |