ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3548A>T (p.Lys1183Ile)

dbSNP: rs16942
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000637591 SCV000759057 uncertain significance Hereditary breast ovarian cancer syndrome 2021-10-15 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 531339). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with isoleucine at codon 1183 of the BRCA1 protein (p.Lys1183Ile). The lysine residue is weakly conserved and there is a moderate physicochemical difference between lysine and isoleucine.
Color Diagnostics, LLC DBA Color Health RCV000776822 SCV000912478 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-16 criteria provided, single submitter clinical testing
Ambry Genetics RCV000776822 SCV001182069 uncertain significance Hereditary cancer-predisposing syndrome 2019-08-28 criteria provided, single submitter clinical testing The p.K1183I variant (also known as c.3548A>T), located in coding exon 9 of the BRCA1 gene, results from an A to T substitution at nucleotide position 3548. The lysine at codon 1183 is replaced by isoleucine, an amino acid with dissimilar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
University of Washington Department of Laboratory Medicine, University of Washington RCV000776822 SCV003850260 likely benign Hereditary cancer-predisposing syndrome 2023-03-23 criteria provided, single submitter curation Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).

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