Submissions for variant NM_003072.5(SMARCA4):c.3095C>A (p.Thr1032Asn)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002881065	SCV003232694	likely pathogenic	Rhabdoid tumor predisposition syndrome 2	2022-10-13	criteria provided, single submitter	clinical testing	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. 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 SMARCA4 protein function. This missense change has been observed in individual(s) with clinical features of Coffin-Siris syndrome (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 1032 of the SMARCA4 protein (p.Thr1032Asn).