Submissions for variant NM_000465.4(BARD1):c.1070T>C (p.Ile357Thr)

dbSNP: rs587781555

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000129571	SCV000184353	likely benign	Hereditary cancer-predisposing syndrome	2018-01-12	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae	RCV000228197	SCV000284893	uncertain significance	Familial cancer of breast	2023-06-27	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 141178). This variant has not been reported in the literature in individuals affected with BARD1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 357 of the BARD1 protein (p.Ile357Thr). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 Diagnostics, LLC DBA Color Health	RCV000129571	SCV000688091	uncertain significance	Hereditary cancer-predisposing syndrome	2023-12-05	criteria provided, single submitter	clinical testing	This missense variant replaces isoleucine with threonine at codon 357 of the BARD1 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. This variant has not been reported in individuals affected with BARD1-related disorders 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.
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000129571	SCV004014934	uncertain significance	Hereditary cancer-predisposing syndrome	2023-03-21	criteria provided, single submitter	clinical testing
GeneDx	RCV003327369	SCV004034340	uncertain significance	not provided	2023-09-06	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge