ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.4636G>C (p.Asp1546His) (rs28897691)

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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 RCV000573632 SCV000661010 uncertain significance Hereditary cancer-predisposing syndrome 2016-03-09 criteria provided, single submitter clinical testing Insufficient or conflicting evidence;In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Invitae RCV001054471 SCV001218787 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-12-23 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with histidine at codon 1546 of the BRCA1 protein (p.Asp1546His). The aspartic acid residue is moderately conserved and there is a moderate physicochemical difference between aspartic acid and histidine. This variant is present in population databases (rs28897691, ExAC 0.01%). This variant has not been reported in the literature in individuals with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 479201). 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.
Color RCV000573632 SCV001348219 uncertain significance Hereditary cancer-predisposing syndrome 2020-02-28 criteria provided, single submitter clinical testing

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