Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000219042 | SCV000277730 | likely benign | Hereditary cancer-predisposing syndrome | 2024-06-24 | 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. |
| Labcorp Genetics |
RCV000474211 | SCV000545576 | uncertain significance | Familial cancer of breast | 2024-05-22 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 572 of the BARD1 protein (p.Leu572Phe). This variant is present in population databases (rs772222117, gnomAD 0.0009%). This missense change has been observed in individual(s) with colorectal cancer (PMID: 28135145). ClinVar contains an entry for this variant (Variation ID: 233371). 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. |
| Gene |
RCV000767169 | SCV000566394 | uncertain significance | not provided | 2017-05-05 | criteria provided, single submitter | clinical testing | This variant is denoted BARD1 c.1714C>T at the cDNA level, p.Leu572Phe (L572F) at the protein level, and results in the change of a Leucine to a Phenylalanine (CTT>TTT). This variant has been reported in an individual with colorectal cancer (Yurgelun 2017). BARD1 Leu572Phe was not observed at a significant allele frequency in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Leucine and Phenylalanine share similar properties, this is considered a conservative amino acid substitution. BARD1 Leu572Phe occurs at a position where amino acids with properties similar to Leucine are tolerated across species and is located in the BRCT1 domain (Fox 2008, UniProt). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether BARD1 Leu572Phe is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000767169 | SCV000600182 | uncertain significance | not provided | 2020-05-23 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV000219042 | SCV000688152 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-04-03 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV000474211 | SCV004217239 | uncertain significance | Familial cancer of breast | 2023-06-30 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV000474211 | SCV005655823 | uncertain significance | Familial cancer of breast | 2024-02-20 | criteria provided, single submitter | clinical testing |