Submissions for variant NM_007294.3(BRCA1):c.4574A>G (p.Gln1525Arg) (rs786203386)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000166668	SCV000217473	uncertain significance	Hereditary cancer-predisposing syndrome	2014-10-28	criteria provided, single submitter	clinical testing	Lines of evidence used in support of classification: Insufficient or conflicting evidence
GeneDx	RCV000482227	SCV000567291	uncertain significance	not provided	2015-07-17	criteria provided, single submitter	clinical testing	This variant is denoted BRCA1 c.4574A>G at the cDNA level, p.Gln1525Arg (Q1525R) at the protein level, and results in the change of a Glutamine to an Arginine (CAA>CGA). Using alternate nomenclature, this variant would be defined as BRCA1 4693A>G. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Gln1525Arg 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 Glutamine and Arginine differ in some properties, this is considered a semi-conservative amino acid substitution. BRCA1 Gln1525Arg occurs at a position that is not conserved and is not located in a known functional domain (UniProt). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether BRCA1 Gln1525Arg is pathogenic or benign. We consider it to be a variant of uncertain significance.