Submissions for variant NM_003919.3(SGCE):c.1195C>T (p.Pro399Ser)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002908695	SCV003252485	uncertain significance	Myoclonic dystonia 11	2023-10-29	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 399 of the SGCE protein (p.Pro399Ser). This variant is present in population databases (rs747427574, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with SGCE-related conditions. ClinVar contains an entry for this variant (Variation ID: 2045520). 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) performed at Invitae indicates that this missense variant is not expected to disrupt SGCE protein function with a negative predictive value of 80%. 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	RCV005239533	SCV005885433	uncertain significance	not specified	2025-02-21	criteria provided, single submitter	clinical testing	Variant summary: SGCE c.1195C>T (p.Pro399Ser) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251256 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.1195C>T in individuals affected with Myoclonic Dystonia 11 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 2045520). Based on the evidence outlined above, the variant was classified as uncertain significance.