Submissions for variant NM_000465.4(BARD1):c.1087T>A (p.Ser363Thr)

dbSNP: rs1064794985

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000486796	SCV000570344	uncertain significance	not provided	2016-05-13	criteria provided, single submitter	clinical testing	This variant is denoted BARD1 c.1087T>A at the cDNA level, p.Ser363Thr (S363T) at the protein level, and results in the change of a Serine to a Threonine (TCT>ACT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BARD1 Ser363Thr was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Serine and Threonine share similar properties, this is considered a conservative amino acid substitution. BARD1 Ser363Thr occurs at a position that is not conserved and is not located in a known functional domain (UniProt). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether BARD1 Ser363Thr is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae	RCV000818162	SCV000958761	uncertain significance	Familial cancer of breast	2023-08-16	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 363 of the BARD1 protein (p.Ser363Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BARD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 421217). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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	RCV001187840	SCV001354729	uncertain significance	Hereditary cancer-predisposing syndrome	2024-01-05	criteria provided, single submitter	clinical testing	This missense variant replaces serine with threonine at codon 363 of the BARD1 protein. Computational prediction suggests that this variant may not impact protein structure and function. 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.
Ambry Genetics	RCV001187840	SCV002729726	uncertain significance	Hereditary cancer-predisposing syndrome	2021-01-29	criteria provided, single submitter	clinical testing	The p.S363T variant (also known as c.1087T>A), located in coding exon 4 of the BARD1 gene, results from a T to A substitution at nucleotide position 1087. The serine at codon 363 is replaced by threonine, an amino acid with similar properties. This amino acid position is 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.