Submissions for variant NM_007294.3(BRCA1):c.100C>T (p.Pro34Ser) (rs1064793357)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000478465	SCV000565896	uncertain significance	not provided	2015-03-09	criteria provided, single submitter	clinical testing	This variant is denoted BRCA1 c.100C>T at the cDNA level, p.Pro34Ser (P34S) at the protein level, and results in the change of a Proline to a Serine (CCT>TCT). Using alternate nomenclature, this variant would be defined as BRCA1 219C>T. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Pro34Ser 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 Proline and Serine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA1 Pro34Ser occurs at a position that is conserved across species and is located within the RING-type zinc finger domain and BARD1 interaction domain (Roy 2012). 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 Pro34Ser is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics	RCV000561610	SCV000668432	uncertain significance	Hereditary cancer-predisposing syndrome	2016-07-12	criteria provided, single submitter	clinical testing	Lines of evidence used in support of classification: Insufficient evidence