ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3681A>T (p.Gln1227His) (rs730881488)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159980 SCV000210153 uncertain significance not provided 2016-04-20 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.3681A>T at the cDNA level, p.Gln1227His (Q1227H) at the protein level, and results in the change of a Glutamine to a Histidine (CAA>CAT). Using alternate nomenclature, this variant would be defined as BRCA1 3800A>T. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Gln1227His was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Glutamine and Histidine differ in some properties, this is considered a semi-conservative amino acid substitution. BRCA1 Gln1227His occurs at a position that is conserved in mammals and is not located in a known functional domain. 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 Gln1227His is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000564237 SCV000673064 uncertain significance Hereditary cancer-predisposing syndrome 2017-05-11 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence

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