ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.93C>G (p.Ile31Met) (rs80357000)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000444279 SCV000516769 likely benign not specified 2016-10-10 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Integrated Genetics/Laboratory Corporation of America RCV000588671 SCV000699320 uncertain significance not provided 2016-06-08 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.93C>G (p.Ile31Met) variant involves the alteration of a non-conserved nucleotide and results in a replacement of an Isoleucine located in the central RING domain of BRCA1 with a Methionine. 2/3 in silico tools predict a damaging outcome (SNPs&GO and mutation taster not captured due to low reliability index) for this substitution. This variant was found in 1/112524 control chromosomes at a frequency of 0.0000089, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA1 variant (0.0010005). It was reported in three probands from HBOC families, however without co-segregation and co-occurrence information, therefore these occurrences do not allow establishment of a cause effect relationship between the variant and the disease. Functional studies demonstrated the variant to be proficient in BARD1 and UbcH5a binding, to be radiation resistant and to decrease E3 activity of BRCA1. Most importantly, the variant was shown not to have a significant impact on homology directed repair activity of BRCA1 which is essential for its tumor suppressing function. The functional studies indicate the variant to be in the neutral spectrum; however, due to lack of stronger clinical information about variant carries, the variant was classified as a variant of uncertain significance (VUS) until additional information becomes available.
Color RCV000775197 SCV000909423 likely benign Hereditary cancer-predisposing syndrome 2018-02-22 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000111750 SCV000144275 uncertain significance Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing

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