Submissions for variant NM_007294.4(BRCA1):c.101del (p.Pro34fs)

dbSNP: rs80357750

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000111768	SCV000299404	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2016-09-08	reviewed by expert panel	curation	Variant allele predicted to encode a truncated non-functional protein.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000496845	SCV000698828	pathogenic	Hereditary breast ovarian cancer syndrome	2017-01-06	criteria provided, single submitter	clinical testing	Variant summary: The BRCA1 c.101delC (p.Pro34Leufs) variant, alternatively also known as 220delC, results in a premature termination codon, predicted to cause a truncated or absent BRCA1 protein due to nonsense mediated decay (NMD), which is the known disease mechanism in HBOC. If the variant escapes NMD, it is expected to truncate substantial part of RING domain and truncate S-R and BRCT domains (InterPro). Truncations downstream of this position have been classified as pathogenic by our laboratory and others (e.g. p.Gln60X, p.Glu143X, p.Trp1815X, etc.). This variant is absent in 113688 control chromosomes from ExAC. In addition, multiple clinical diagnostic laboratories/reputable databases have classified this variant as pathogenic. The variant of interest has not, to our knowledge, been reported in affected individuals via publications. It has been reported in at least two HBOC patients by clinical labs in ClinVar. Taken together, this variant is classified as Pathogenic.
Ambry Genetics	RCV002362680	SCV002666312	pathogenic	Hereditary cancer-predisposing syndrome	2017-02-24	criteria provided, single submitter	clinical testing	The c.101delC variant, located in coding exon 2 of the BRCA1 gene, results from a deletion of one nucleotide at nucleotide position 101, causing a translational frameshift with a predicted alternate stop codon (p.P34Lfs*16). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Breast Cancer Information Core (BIC) (BRCA1)	RCV000111768	SCV000144299	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2003-12-23	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496845	SCV000587010	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research