Submissions for variant NM_005901.6(SMAD2):c.953A>G (p.Asn318Ser)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002765699	SCV003010111	uncertain significance	not provided	2024-04-02	criteria provided, single submitter	clinical testing	This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 318 of the SMAD2 protein (p.Asn318Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of SMAD2-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 1974591). 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 SMAD2 protein function. This variant disrupts the p.Asn318 amino acid residue in SMAD2. Other variant(s) that disrupt this residue have been observed in individuals with SMAD2-related conditions (PMID: 29967133; Invitae), which suggests that this may be a clinically significant amino acid residue. 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.