ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.1199A>G (p.Asp400Gly)

dbSNP: rs1555592245
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000509770 SCV000608204 uncertain significance Hereditary cancer-predisposing syndrome 2022-08-01 criteria provided, single submitter clinical testing The p.D400G variant (also known as c.1199A>G), located in coding exon 9 of the BRCA1 gene, results from an A to G substitution at nucleotide position 1199. The aspartic acid at codon 400 is replaced by glycine, an amino acid with 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 RCV001040180 SCV001203741 uncertain significance Hereditary breast ovarian cancer syndrome 2021-09-29 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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: 441494). This missense change has been observed in individual(s) with clinical features of BRCA1-related conditions (PMID: 21520333). This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with glycine at codon 400 of the BRCA1 protein (p.Asp400Gly). The aspartic acid residue is moderately conserved and there is a moderate physicochemical difference between aspartic acid and glycine.
University of Washington Department of Laboratory Medicine, University of Washington RCV000509770 SCV003846110 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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