ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.4339C>A (p.Gln1447Lys) (rs80357067)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000759540 SCV000210174 uncertain significance not provided 2014-06-05 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.4339C>A at the cDNA level, p.Gln1447Lys (Q1447K) at the protein level, and results in the change of a Glutamine to a Lysine (CAA>AAA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Gln1447Lys 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 Glutamine and Lysine differ in some properties, this is considered a semi-conservative amino acid substitution. BRCA1 Gln1447Lys occurs at a position that is well conserved across mammalian species with Lysine being the naturally occurring amino acid in one mammal. It is not located in a known functional domain. In addition, in silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available information, it is unclear whether BRCA1 Gln1447Lys is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000457370 SCV000549315 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-07-27 criteria provided, single submitter clinical testing This sequence change replaces glutamine with lysine at codon 1447 of the BRCA1 protein (p.Gln1447Lys). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and lysine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BRCA1-related disease. ClinVar contains an entry for this variant (Variation ID: 182161). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000570241 SCV000660998 uncertain significance Hereditary cancer-predisposing syndrome 2016-09-25 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759540 SCV000888919 uncertain significance not provided 2018-06-23 criteria provided, single submitter clinical testing
Color RCV000570241 SCV000911083 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-26 criteria provided, single submitter clinical testing

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