Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000130446 | SCV000185310 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-02-18 | criteria provided, single submitter | clinical testing | The p.N112D variant (also known as c.334A>G), located in coding exon 5 of the BRCA1 gene, results from an A to G substitution at nucleotide position 334. The asparagine at codon 112 is replaced by aspartic acid, 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. |
Color Diagnostics, |
RCV000130446 | SCV000909414 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-11-12 | criteria provided, single submitter | clinical testing | This missense variant replaces asparagine with aspartic acid at codon 112 of the BRCA1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Invitae | RCV001236823 | SCV001409561 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2021-08-30 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine with aspartic acid at codon 112 of the BRCA1 protein (p.Asn112Asp). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 141794). 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. 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. |
Gene |
RCV001555145 | SCV001776510 | uncertain significance | not provided | 2019-05-20 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge |