ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.172C>A (p.Pro58Thr) (rs397508904)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159934 SCV000210066 uncertain significance not provided 2015-05-19 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.172C>A at the cDNA level, p.Pro58Thr (P58T) at the protein level, and results in the change of a Proline to a Threonine (CCT>ACT). This variant, also known as BRCA1 c.291C>A using alternate nomenclature, has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Pro58Thr 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 Proline and Threonine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA1 Pro58Thr occurs at a position that is not conserved and is located within the RING-type zinc finger domain (UniProt, Narod 2004). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether BRCA1 Pro58Thr is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000571136 SCV000660984 uncertain significance Hereditary cancer-predisposing syndrome 2017-08-08 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Color RCV000571136 SCV000688346 uncertain significance Hereditary cancer-predisposing syndrome 2020-03-13 criteria provided, single submitter clinical testing
Invitae RCV001036738 SCV001200116 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-12-23 criteria provided, single submitter clinical testing This sequence change replaces proline with threonine at codon 58 of the BRCA1 protein (p.Pro58Thr). The proline residue is moderately conserved and there is a small physicochemical difference between proline and threonine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 182122). This variant has been reported not to substantially affect BRCA1 protein function (PMID: 30209399). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Brotman Baty Institute,University of Washington RCV001077106 SCV001242979 not provided Breast-ovarian cancer, familial 1 no assertion provided in vitro

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