ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9354G>A (p.Met3118Ile) (rs1555289559)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000799670 SCV000939344 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-09-05 criteria provided, single submitter clinical testing This sequence change replaces methionine with isoleucine at codon 3118 of the BRCA2 protein (p.Met3118Ile). The methionine residue is weakly conserved and there is a small physicochemical difference between methionine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with breast cancer in the Leiden Open-source Variation Database (PMID: 21520333). However, in one individual a pathogenic allele was also identified in BRCA2, which suggests that this c.9354G>A variant was not the primary cause of disease. ClinVar contains an entry for this variant (Variation ID: 439018). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000507949 SCV000600856 uncertain significance not specified 2017-04-17 criteria provided, single submitter clinical testing

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