ClinVar Miner

Submissions for variant NM_152743.4(BRAT1):c.1378C>T (p.Pro460Ser)

gnomAD frequency: 0.00004  dbSNP: rs373935601
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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 RCV000550295 SCV000652224 uncertain significance Neonatal-onset encephalopathy with rigidity and seizures 2024-04-05 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 460 of the BRAT1 protein (p.Pro460Ser). This variant is present in population databases (rs373935601, gnomAD 0.009%). 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: 472938). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on BRAT1 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.
Baylor Genetics RCV000550295 SCV001526220 uncertain significance Neonatal-onset encephalopathy with rigidity and seizures 2018-04-02 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Ambry Genetics RCV004965562 SCV005548512 uncertain significance Inborn genetic diseases 2024-11-22 criteria provided, single submitter clinical testing The c.1378C>T (p.P460S) alteration is located in exon 10 (coding exon 9) of the BRAT1 gene. This alteration results from a C to T substitution at nucleotide position 1378, causing the proline (P) at amino acid position 460 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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