ClinVar Miner

Submissions for variant NM_152743.4(BRAT1):c.1555T>C (p.Ser519Pro)

gnomAD frequency: 0.00001  dbSNP: rs1300644959
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000689175 SCV000816815 uncertain significance Neonatal-onset encephalopathy with rigidity and seizures 2021-10-25 criteria provided, single submitter clinical testing This sequence change replaces serine with proline at codon 519 of the BRAT1 protein (p.Ser519Pro). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with BRAT1-related conditions. 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 disruptive. 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.
GeneDx RCV002245588 SCV002513757 likely pathogenic not provided 2024-03-13 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV003278996 SCV003955542 uncertain significance Inborn genetic diseases 2023-03-24 criteria provided, single submitter clinical testing The c.1555T>C (p.S519P) alteration is located in exon 12 (coding exon 11) of the BRAT1 gene. This alteration results from a T to C substitution at nucleotide position 1555, causing the serine (S) at amino acid position 519 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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