ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.272T>G (p.Phe91Cys)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002453236 SCV002738706 uncertain significance Hereditary cancer-predisposing syndrome 2016-01-05 criteria provided, single submitter clinical testing The p.F91C variant (also known as c.272T>G), located in coding exon 3 of the CDH1 gene, results from a T to G substitution at nucleotide position 272. The phenylalanine at codon 91 is replaced by cysteine, an amino acid with highly dissimilar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6498 samples (12996 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 175000 alleles tested) in our clinical cohort. Based on protein sequence alignment, this amino acid position is poorly 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 p.F91C remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003624496 SCV004385124 uncertain significance Hereditary diffuse gastric adenocarcinoma 2023-06-05 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 1795287). This variant has not been reported in the literature in individuals affected with CDH1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces phenylalanine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 91 of the CDH1 protein (p.Phe91Cys).

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