Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000633773 | SCV000755046 | uncertain significance | Gastrointestinal stromal tumor | 2023-10-25 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 951 of the KIT protein (p.Val951Ile). This variant is present in population databases (rs745651409, gnomAD 0.002%). 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: 528552). 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 | RCV001016767 | SCV001177762 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-09-19 | criteria provided, single submitter | clinical testing | The p.V951I variant (also known as c.2851G>A), located in coding exon 21 of the KIT gene, results from a G to A substitution at nucleotide position 2851. The valine at codon 951 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Prevention |
RCV004748871 | SCV005352505 | uncertain significance | KIT-related disorder | 2024-09-05 | no assertion criteria provided | clinical testing | The KIT c.2851G>A variant is predicted to result in the amino acid substitution p.Val951Ile. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0018% of alleles in individuals of European (Non-Finnish) descent in gnomAD. This variant is interpreted as a variant of uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/528552/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |