Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000569978 | SCV000668926 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-10 | criteria provided, single submitter | clinical testing | The p.I1231M variant (also known as c.3693A>G), located in coding exon 19 of the BRIP1 gene, results from an A to G substitution at nucleotide position 3693. The isoleucine at codon 1231 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is not 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. |
Mendelics | RCV000709520 | SCV000839344 | uncertain significance | Fanconi anemia complementation group J | 2018-07-02 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000989970 | SCV001140732 | uncertain significance | Familial cancer of breast | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001055410 | SCV001219798 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2023-12-18 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1231 of the BRIP1 protein (p.Ile1231Met). This variant is present in population databases (no rsID available, gnomAD 0.004%). This missense change has been observed in individual(s) with breast cancer (PMID: 35264596). ClinVar contains an entry for this variant (Variation ID: 483173). 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. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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. |
Laboratorio de Genetica e Diagnostico Molecular, |
RCV000989970 | SCV003807202 | uncertain significance | Familial cancer of breast | 2022-08-12 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PM2 moderated, BP4 supporting |