ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.61C>G (p.Leu21Val)

gnomAD frequency: 0.00003  dbSNP: rs863224729
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen CDH1 Variant Curation Expert Panel RCV003328279 SCV001437603 uncertain significance CDH1-related diffuse gastric and lobular breast cancer syndrome 2023-08-21 reviewed by expert panel curation The c.61C>G (p.Leu21Val) variant results in a non-synonymous amino acid change in exon 2. This variant is present in 5 of 188,446 alleles (0.00003) in gnomAD, present exclusively in the East Asian subpopulation with 5 of 12,882 alleles (0.00039). This variant has been observed in at least three individuals without DGC, SRC tumour or LBC and whose families do not suggest HDGC (BS2_supporting). In summary, the clinical significance of this variant is uncertain based on ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): BS2_supporting.
Ambry Genetics RCV000222019 SCV000273623 uncertain significance Hereditary cancer-predisposing syndrome 2022-11-04 criteria provided, single submitter clinical testing The p.L21V variant (also known as c.61C>G), located in coding exon 2 of the CDH1 gene, results from a C to G substitution at nucleotide position 61. The leucine at codon 21 is replaced by valine, an amino acid with highly similar properties. This amino acid position is 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000456561 SCV000545425 uncertain significance Hereditary diffuse gastric adenocarcinoma 2023-11-25 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 21 of the CDH1 protein (p.Leu21Val). This variant is present in population databases (no rsID available, gnomAD 0.04%). This missense change has been observed in individual(s) with CDH1-related conditions (PMID: 30287823, 36436516). ClinVar contains an entry for this variant (Variation ID: 230175). 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.
Color Diagnostics, LLC DBA Color Health RCV000222019 SCV001344543 uncertain significance Hereditary cancer-predisposing syndrome 2021-10-26 criteria provided, single submitter clinical testing This missense variant replaces leucine with valine at codon 21 of the CDH1 protein. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 5/188446 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
European Reference Network on Genetic Tumour Risk Syndromes (ERN-GENTURIS), i3s - Instituto de Investigação e Inovação em Saúde, University of Porto RCV000456561 SCV003926893 uncertain significance Hereditary diffuse gastric adenocarcinoma 2022-08-01 criteria provided, single submitter clinical testing PS4_Supporting; BS2_Supporting (PMID: 30311375)
Baylor Genetics RCV004567516 SCV005060148 uncertain significance Familial cancer of breast 2023-11-07 criteria provided, single submitter clinical testing

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