Submissions for variant NM_001365999.1(SZT2):c.6343C>G (p.Pro2115Ala)

gnomAD frequency: 0.00073  dbSNP: rs147309177

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000863287	SCV001003923	likely benign	not provided	2025-01-30	criteria provided, single submitter	clinical testing
New York Genome Center	RCV004799243	SCV001431142	uncertain significance	Developmental and epileptic encephalopathy, 18	2022-02-25	criteria provided, single submitter	clinical testing
GeneDx	RCV000863287	SCV001810755	uncertain significance	not provided	2022-02-23	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics	RCV002352511	SCV002660412	uncertain significance	Inborn genetic diseases	2018-10-29	criteria provided, single submitter	clinical testing	The p.P2058A variant (also known as c.6172C>G), located in coding exon 44 of the SZT2 gene, results from a C to G substitution at nucleotide position 6172. The proline at codon 2058 is replaced by alanine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003987724	SCV004804087	uncertain significance	not specified	2024-01-03	criteria provided, single submitter	clinical testing	Variant summary: C1orf84 c.6172C>G (p.Pro2058Ala) results in a non-conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00024 in 282628 control chromosomes (gnomAD). To our knowledge, no occurrence of c.6172C>G in individuals affected with Early Infantile Epileptic Encephalopathy 18 and no experimental evidence demonstrating its impact on protein function have been reported. Four submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 and classified this variant as uncertain significance (n=3) and likely benign (n=1). Based on the evidence outlined above, the variant was classified as uncertain significance.
PreventionGenetics, part of Exact Sciences	RCV003928353	SCV004746006	likely benign	SZT2-related disorder	2023-03-14	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).