ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3143G>T (p.Gly1048Val)

dbSNP: rs80356899
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000112009 SCV001161501 benign Breast-ovarian cancer, familial, susceptibility to, 1 2019-06-18 reviewed by expert panel curation IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.000314
GeneDx RCV000590820 SCV000210142 uncertain significance not provided 2015-08-04 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.3143G>T at the cDNA level, p.Gly1048Val (G1048V) at the protein level, and results in the change of a Glycine to a Valine (GGT>GTT). Using alternate nomenclature, this variant would be defined as BRCA1 3262G>T. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Gly1048Val 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 Glycine and Valine share similar properties, this is considered a conservative amino acid substitution. BRCA1 Gly1048Val occurs at a position that is not conserved and is located within the DNA-binding domain and the region of interaction with RAD51 and BASC (UniProt). 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 Gly1048Val is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000214911 SCV000277268 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-11 criteria provided, single submitter clinical testing The p.G1048V variant (also known as c.3143G>T), located in coding exon 9 of the BRCA1 gene, results from a G to T substitution at nucleotide position 3143. The glycine at codon 1048 is replaced by valine, an amino acid with dissimilar 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, LLC DBA Color Health RCV000214911 SCV000683087 uncertain significance Hereditary cancer-predisposing syndrome 2022-09-26 criteria provided, single submitter clinical testing This missense variant replaces glycine with valine at codon 1048 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). To our knowledge, functional studies have not been reported for this variant. A multifactorial analysis has reported co-occurrence and family history likelihood ratios of 1.1391 and 0.0135, respectively (PMID: 31131967). This variant has been identified in 1/251002 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Although there is a suspicion that this variant may not be associated with disease, additional studies are necessary to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000590820 SCV000699006 uncertain significance not provided 2016-02-01 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000590820 SCV002049680 likely benign not provided 2021-10-21 criteria provided, single submitter clinical testing
Invitae RCV002514243 SCV003242288 likely benign Hereditary breast ovarian cancer syndrome 2024-01-20 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000112009 SCV000144649 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 1 2004-02-20 no assertion criteria provided clinical testing

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