Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Evidence- |
RCV000030990 | SCV000299592 | 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 | RCV000213424 | SCV000278779 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-01-09 | criteria provided, single submitter | clinical testing | The c.1389_1390delAAinsG pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from the deletion of two nucleotides and insertion of one nucleotide causing a translational frameshift with a predicted alternate stop codon (p.T464Pfs*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 |
RCV000487351 | SCV000566059 | pathogenic | not provided | 2015-03-20 | criteria provided, single submitter | clinical testing | This combined deletion and insertion is denoted c.1389_1390delAAinsG at the cDNA level and p.Thr464ProfsX11 (T464PfsX11) at the protein level. Using alternate nomenclature, this variant would be defined as c.1508delAAinsG. The normal sequence, with the bases that are deleted and inserted in brackets, is GGAA[delAA][insG]CCTA. The variant causes a frameshift, which changes a Threonine to a Proline at codon 464, and creates a premature stop codon at position 11 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. We consider BRCA1 c.1389_1390delAAinsG to be pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000462415 | SCV000918677 | pathogenic | Hereditary breast ovarian cancer syndrome | 2018-04-02 | criteria provided, single submitter | clinical testing | Variant summary: BRCA1 c.1389_1390delinsG (p.Thr464ProfsX11) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (eg. c.1480C>T (p.Gln494X), c.1492delC (p.Leu498fsX5), and c.1508delA (p.Lys503fsX29)). The variant was absent in 245916 control chromosomes (gnomAD). The variant, c.1389_1390delinsG, has not been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer. However, other variants such as c.1390delA (legacy names: c.1387delA, 1506delA) and c.1386delA (legacy name: 1505delG) that cause the same frameshift mutation have been reported in affected HBOC patients (Couch_1996, Peyrat_1998, Rebbeck_2016). Multiple ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as "pathogenic." Based on the evidence outlined above, the variant was classified as pathogenic. |
| Sharing Clinical Reports Project |
RCV000030990 | SCV000053582 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2010-12-23 | no assertion criteria provided | clinical testing | |
| Breast Cancer Information Core |
RCV000030990 | SCV000144078 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2001-10-29 | no assertion criteria provided | clinical testing |