Submissions for variant NM_152743.4(BRAT1):c.1710del (p.Gln571fs)

dbSNP: rs756489141

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001008449	SCV001168220	likely pathogenic	not provided	2022-06-28	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation, as the last 251 amino acids are replaced with 31 different amino acids, and other loss-of-function variants have been reported downstream in HGMD.; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge
Invitae	RCV001237971	SCV001410764	likely pathogenic	Neonatal-onset encephalopathy with rigidity and seizures	2023-10-16	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln571Serfs*32) in the BRAT1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 251 amino acid(s) of the BRAT1 protein. This variant is present in population databases (rs756489141, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with BRAT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 817329). This variant disrupts the C-terminus of the BRAT1 protein. Other variant(s) that disrupt this region (p.Trp619*, p.Ser747Thrfs*36, p.Phe709Thrfs*17) have been observed in individuals with BRAT1-related conditions (PMID: 27480663, 28752061). This suggests that this may be a clinically significant region of the protein. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Revvity Omics, Revvity	RCV001008449	SCV002022792	pathogenic	not provided	2019-07-15	criteria provided, single submitter	clinical testing