ClinVar Miner

Submissions for variant NM_000222.3(KIT):c.1351T>C (p.Ser451Pro)

gnomAD frequency: 0.00006  dbSNP: rs145183977
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000462044 SCV000550052 uncertain significance Gastrointestinal stromal tumor 2024-11-27 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 451 of the KIT protein (p.Ser451Pro). This variant is present in population databases (rs145183977, gnomAD 0.005%). 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: 409718). 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 RCV001011082 SCV001171363 likely benign Hereditary cancer-predisposing syndrome 2024-04-09 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Sema4, Sema4 RCV001011082 SCV002536385 uncertain significance Hereditary cancer-predisposing syndrome 2022-03-18 criteria provided, single submitter curation
Baylor Genetics RCV000462044 SCV004198081 uncertain significance Gastrointestinal stromal tumor 2024-03-15 criteria provided, single submitter clinical testing
GeneDx RCV004591320 SCV005078776 uncertain significance not provided 2023-10-05 criteria provided, single submitter clinical testing Has been reported in a patient with melanoma, colorectal cancer, and systemic mastocytosis (Pritchard et al., 2018); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 29641532)
PreventionGenetics, part of Exact Sciences RCV003409631 SCV004113372 uncertain significance KIT-related disorder 2024-06-28 no assertion criteria provided clinical testing The KIT c.1351T>C variant is predicted to result in the amino acid substitution p.Ser451Pro. This variant has been reported in a cohort study of individuals with cutaneous melanoma and at least two independent additional primary cancers (Supplemental Data, Pritchard et al. 2018. PubMed ID: 29641532). This variant is reported in 0.0047% of alleles in individuals of European (Non-Finnish) descent in gnomAD and interpreted as uncertain in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/409718/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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