Submissions for variant NM_001365999.1(SZT2):c.8177C>G (p.Thr2726Ser)

gnomAD frequency: 0.00055  dbSNP: rs145882968

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000459918	SCV000553351	likely benign	not provided	2025-01-27	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002313181	SCV000849251	benign	Inborn genetic diseases	2017-03-29	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
GeneDx	RCV000459918	SCV001783914	likely benign	not provided	2021-03-23	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003457687	SCV004178000	likely benign	Developmental and epileptic encephalopathy, 18	2023-04-11	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV005407127	SCV006071388	uncertain significance	not specified	2025-03-25	criteria provided, single submitter	clinical testing	Variant summary: SZT2 c.8006C>G (p.Thr2669Ser) results in a conservative amino acid change in the encoded protein sequence. Four of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00043 in 247450 control chromosomes in the gnomAD database, including 1 homozygotes. This frequency is not significantly higher than estimated for a pathogenic variant in SZT2 causing Early Infantile Epileptic Encephalopathy 18, allowing no conclusion about variant significance. To our knowledge, no occurrence of c.8006C>G in individuals affected with Early Infantile Epileptic Encephalopathy 18 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 411936). Based on the evidence outlined above, the variant was classified as uncertain significance.
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille	RCV001252126	SCV001427876	uncertain significance	Intellectual disability	2019-01-01	no assertion criteria provided	clinical testing