Submissions for variant NM_000059.4(BRCA2):c.3407_3414delinsCATTGCAC (p.Ile1136_Gln1138delinsThrLeuHis)

Minimum review status:		Collection method:
Minimum conflict level: Report conflict between different conditions
		ClinVar version:

Total submissions: 2

Download table as spreadsheet

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000481513	SCV000566152	uncertain significance	not provided	2015-03-27	criteria provided, single submitter	clinical testing	This variant is denoted as BRCA2 c.3407_3414delTATTGCAGinsCATTGCAC at the cDNA level and p.I1136_Q1138delinsTLH at the protein level. The normal sequence, with the bases that are deleted and inserted in brackets, is TACA[delTATTGCAG][insCATTGCAC]AAGA. The deletion and insertion results in the replacement of an Isoleucine residue and a Glutamine residue with a Threonine residue and Histidine residue, respectively, creating two missense changes: Ile1136Thr and Gln1138His. The Leucine at position 1137 remains unchanged by this deletion and insertion. Neither this combined variant nor the individual missense changes have been reported in the literature as pathogenic or benign, to our knowledge. BRCA2 I1136_Q1138delinsTLH 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 Isoleucine and Threonine differ in polarity, charge, size or other properties, it is considered a non-conservative amino acid substitution whereas Glutamine and Histidine differ in some properties and is considered a semi-conservative amino acid substitution. This variant alters positions that are not conserved across species and is not located in a known functional domain (UniProt). Based on currently available information, it is unclear whether this variant is pathogenic or benign. We consider it to be a variant of uncertain significance.
University of Washington Department of Laboratory Medicine, University of Washington	RCV003157565	SCV003847515	likely benign	Hereditary cancer-predisposing syndrome	2023-03-23	criteria provided, single submitter	curation	Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.