ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.1248G>C (p.Leu416Phe)

gnomAD frequency: 0.00002  dbSNP: rs772622537
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000793776 SCV000933148 uncertain significance Hereditary diffuse gastric adenocarcinoma 2023-04-12 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with CDH1-related conditions. 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. 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 640697). This variant is present in population databases (rs772622537, gnomAD 0.01%). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 416 of the CDH1 protein (p.Leu416Phe).
Ambry Genetics RCV002388423 SCV002674197 uncertain significance Hereditary cancer-predisposing syndrome 2022-08-09 criteria provided, single submitter clinical testing The p.L416F variant (also known as c.1248G>C), located in coding exon 9 of the CDH1 gene, results from a G to C substitution at nucleotide position 1248. The leucine at codon 416 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is conserved. 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.

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