Submissions for variant NM_007294.4(BRCA1):c.3392_3393delinsTA (p.Asp1131Val)

dbSNP: rs786203428

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000166729	SCV000217540	uncertain significance	Hereditary cancer-predisposing syndrome	2014-10-23	criteria provided, single submitter	clinical testing	The c.3392_3393delATinsTA variant (also known as p.D1131V or 3511_3512delATinsTA), located in coding exon 9 of the BRCA1 gene, results from an in-frame deletion of AT and insertion of TA between nucleotide positions 3392 and 3393. This results in the substitution of the aspartic acid residue for a valine residue at codon 1131, an amino acid with highly dissimilar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.002% (greater than 64000 alleles tested) in our clinical cohort. This amino acid position is well conserved in available higher vertebrate species. Since supporting evidence is limited at this time, the clinical significance of p.D1131V remains unclear.
University of Washington Department of Laboratory Medicine, University of Washington	RCV000166729	SCV003848022	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).