ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.1508del (p.Lys503fs) (rs80357506)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Breast Cancer Information Core (BIC) (BRCA1) RCV000111634 SCV000144116 pathogenic Breast-ovarian cancer, familial 1 no assertion criteria provided clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000111634 SCV000325087 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000502143 SCV000591338 pathogenic Hereditary breast and ovarian cancer syndrome 2015-08-31 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000111634 SCV000299610 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000484870 SCV000569659 pathogenic not provided 2018-06-27 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA1 is denoted c.1508delA at the cDNA level and p.Lys503SerfsX29 (K503SfsX29) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA1 1627delA. The normal sequence, with the base that is deleted in brackets, is TTAA[delA]GCGT. The deletion causes a frameshift which changes a Lysine to a Serine at codon 503, and creates a premature stop codon at position 29 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA1 c.1508delA has been reported in at least one individual from a hereditary breast/ovarian cancer family (Judkins 2005). We consider this variant to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000502143 SCV000698869 pathogenic Hereditary breast and ovarian cancer syndrome 2016-03-08 criteria provided, single submitter clinical testing Variant summary: This c.1508delA variant causes a frameshift, which alters the proteins amino acid sequence beginning at position 503 and leads to a premature termination codon 29 amino acids downstream. It is predicted to cause a truncated or absent BRCA1 protein. Loss-of-function due to mutations in this gene is an established disease mechanism in HBOC. This variant was not found in 121212 control chromosomes from ExAC but is reported in two individuals affected with HBOC or HBOC-related cancer. One reputable database has classified this variant as pathogenic. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. p.Gln563X, p.Lys654X, p.Ser713X, etc.). Taken together, this variant been classified as pathogenic.

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