ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.5574C>G (p.Ile1858Met)

dbSNP: rs876659941
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000507156 SCV000600428 uncertain significance not specified 2017-02-20 criteria provided, single submitter clinical testing
Ambry Genetics RCV000564494 SCV000661031 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-13 criteria provided, single submitter clinical testing The p.I1858M variant (also known as c.5574C>G), located in coding exon 22 of the BRCA1 gene, results from a C to G substitution at nucleotide position 5574. The isoleucine at codon 1858 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is not well 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.
Invitae RCV000637606 SCV000759072 uncertain significance Hereditary breast ovarian cancer syndrome 2022-08-09 criteria provided, single submitter clinical testing This variant is present in population databases (no rsID available, gnomAD 0.0009%). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function. ClinVar contains an entry for this variant (Variation ID: 438943). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1858 of the BRCA1 protein (p.Ile1858Met).
GeneDx RCV001540362 SCV001758239 uncertain significance not provided 2023-01-17 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Also known as 5693C>G

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