Submissions for variant NM_006772.3(SYNGAP1):c.1025A>C (p.Tyr342Ser)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002923545	SCV003273760	uncertain significance	Intellectual disability, autosomal dominant 5	2024-05-15	criteria provided, single submitter	clinical testing	This sequence change replaces tyrosine, which is neutral and polar, with serine, which is neutral and polar, at codon 342 of the SYNGAP1 protein (p.Tyr342Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SYNGAP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 2062297). 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 SYNGAP1 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV005059090	SCV005726807	uncertain significance	not specified	2024-11-11	criteria provided, single submitter	clinical testing	Variant summary: SYNGAP1 c.1025A>C (p.Tyr342Ser) results in a non-conservative amino acid change located in the C2 domain (IPR000008) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251154 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1025A>C in individuals affected with Intellectual Disability, Autosomal Dominant 5 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 2062297). Based on the evidence outlined above, the variant was classified as uncertain significance.