ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.5186T>A (p.Leu1729Gln) (rs730881496)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000160000 SCV000210204 uncertain significance not provided 2014-05-16 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.5186T>A at the cDNA level, p.Leu1729Gln (L1729Q) at the protein level, and results in the change of a Leucine to a Glutamine (CTG>CAG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Leu1729Gln 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 Leucine and Glutamine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA1 Leu1729Gln occurs at a position that is well conserved among mammals and is located in in the BRCT 1 domain (UniProt). In addition, in silico analyses predict that this variant is probably damaging to protein structure and function. Based on the currently available information, we consider BRCA1 Leu1729Gln to be a variant of uncertain significance.Of note, two deleterious BRCA1 variants on opposite chromosomes (in trans) are expected to be incompatible with life. Therefore, if this variant is in trans with the pathogenic BRCA1 variant, then this variant is likely a polymorphism. Parental or family testing could help determine whether the variant is in cis or trans with the BRCA1 variant.
Ambry Genetics RCV000165263 SCV000215979 uncertain significance Hereditary cancer-predisposing syndrome 2014-08-07 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Counsyl RCV000411989 SCV000488798 uncertain significance Breast-ovarian cancer, familial 1 2016-06-21 criteria provided, single submitter clinical testing

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