Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
RCV000143835 | SCV000300088 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2016-09-08 | reviewed by expert panel | curation | Variant allele predicted to encode a truncated non-functional protein. |
Ambry Genetics | RCV000221513 | SCV000278475 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-06-19 | criteria provided, single submitter | clinical testing | The c.4182_4183dupTC pathogenic mutation, located in coding exon 10 of the BRCA1 gene, results from a duplication of 2 nucleotides at positions 4182 and 4183, causing a translational frameshift with a predicted alternate stop codon (p.Q1395Lfs*11). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
Gene |
RCV000235957 | SCV000292521 | pathogenic | not provided | 2015-11-12 | criteria provided, single submitter | clinical testing | This duplication of 2 nucleotides in BRCA1 is denoted c.4182_4183dupTC at the cDNA level and p.Gln1395LeufsX11 (Q1395LfsX11) at the protein level. The normal sequence, with the bases that are duplicated in braces, is CCAC[TC]AGgt, where the capital letters are exonic and lowercase are intronic. The duplication causes a frameshift, which changes a Glutamine to a Leucine at codon 1395, and creates a premature stop codon at position 11 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA1 c.4182_4183dupTC, also reported as BRCA1 Q1395fs, has been observed in at least one woman with serous ovarian cancer (Yang 2011). We consider this variant to be pathogenic. |
Invitae | RCV001383016 | SCV001582024 | pathogenic | Hereditary breast ovarian cancer syndrome | 2023-06-18 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 55124). This premature translational stop signal has been observed in individual(s) with ovarian cancer (PMID: 21990299). This variant is present in population databases (rs80357742, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Gln1395Leufs*11) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). |
Sharing Clinical Reports Project |
RCV000143835 | SCV000115121 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2012-03-01 | no assertion criteria provided | clinical testing | |
Breast Cancer Information Core |
RCV000143835 | SCV000145006 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2004-11-25 | no assertion criteria provided | clinical testing |