ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.5024C>T (p.Thr1675Ile) (rs150729791)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000228214 SCV000289815 likely benign Hereditary breast and ovarian cancer syndrome 2017-10-06 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000239208 SCV000296456 uncertain significance Breast-ovarian cancer, familial 1 2016-04-21 criteria provided, single submitter clinical testing
GeneDx RCV000256063 SCV000321437 uncertain significance not provided 2017-08-03 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.5024C>T at the cDNA level, p.Thr1675Ile (T1675I) at the protein level, and results in the change of a Threonine to an Isoleucine (ACT>ATT). This variant, also known as BRCA1 5143C>T by alternate nomenclature, has been observed in at least three individuals with personal and/or family history of breast and/or ovarian cancer (Alharbi 2005, Caminsky 2016, Dos Santos Vidal 2016). BRCA1 Thr1675Ile was not observed at a significant allele frequency in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Threonine and Isoleucine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA1 Thr1675Ile occurs at a position that is not conserved and is located in the BRCT1 domain and a region known to interact with multiple proteins (Paul 2014, UniProt). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether BRCA1 Thr1675Ile is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000570967 SCV000660957 uncertain significance Hereditary cancer-predisposing syndrome 2017-05-25 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000570967 SCV000908998 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-22 criteria provided, single submitter clinical testing

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