ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.5555C>T (p.Thr1852Ile) (rs730881502)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000160015 SCV000210231 uncertain significance not provided 2014-04-01 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.5555C>T at the cDNA level, p.Thr1852Ile (T1852I) at the protein level, and results in the change of a Threonine to an Isoleucine (ACC>ATC). This variant was observed in an Indonesian woman with early onset breast cancer and was considered an unclassified variant (Purnomosari 2007). An in vitro study found BRCA1 Thr1852 to be a likely binding site for Chk2FHA, but this needs to be verified by in vivo studies in order to determine any clinical significance (Qin 2003). BRCA1 Thr1852Ile was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Threonine and Isoleucine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution and is likely to affect protein integrity. BRCA1 Thr1852Ile occurs at a position that is moderately conserved across species and is located in the BRCT 2 repeat domain (UniProt). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available information, it is unclear whether BRCA1 Thr1852Ile is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000509851 SCV000607987 uncertain significance Hereditary cancer-predisposing syndrome 2016-05-04 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence

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