ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.1202G>C (p.Gly401Ala) (rs397507184)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131360 SCV000186336 uncertain significance Hereditary cancer-predisposing syndrome 2013-08-19 criteria provided, single submitter clinical testing Insufficient evidence
GeneDx RCV000759491 SCV000292891 uncertain significance not provided 2016-02-01 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.1202G>C at the cDNA level, p.Gly401Ala (G401A) at the protein level, and results in the change of a Glycine to an Alanine (GGG>GCG). Using alternate nomenclature, this variant would be defined as BRCA1 1321G>C. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Gly401Ala 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 Alanine share similar properties, this is considered a conservative amino acid substitution. BRCA1 Gly401Ala occurs at a position that is not conserved and is located in a region known to interact with multiple proteins (Paul 2014). 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 Gly401Ala is pathogenic or benign. We consider it to be a variant of uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759491 SCV000888836 uncertain significance not provided 2018-05-29 criteria provided, single submitter clinical testing
Color RCV000131360 SCV000909387 uncertain significance Hereditary cancer-predisposing syndrome 2019-01-04 criteria provided, single submitter clinical testing
Invitae RCV001215282 SCV001387017 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-07-09 criteria provided, single submitter clinical testing This sequence change replaces glycine with alanine at codon 401 of the BRCA1 protein (p.Gly401Ala). The glycine residue is weakly conserved and there is a small physicochemical difference between glycine and alanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 91541). 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, but 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.
Sharing Clinical Reports Project (SCRP) RCV000077058 SCV000108855 uncertain significance Breast-ovarian cancer, familial 1 2009-12-22 no assertion criteria provided clinical testing

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