Submissions for variant NM_000168.6(GLI3):c.2048C>T (p.Thr683Ile)

dbSNP: rs979364849

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV001198781	SCV001369776	uncertain significance	Pallister-Hall syndrome	2019-02-14	criteria provided, single submitter	clinical testing	This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PM2,PPP3.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003770220	SCV004578059	uncertain significance	Greig cephalopolysyndactyly syndrome; Pallister-Hall syndrome	2023-09-13	criteria provided, single submitter	clinical testing	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. 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 expected to disrupt GLI3 protein function. ClinVar contains an entry for this variant (Variation ID: 931841). This variant has not been reported in the literature in individuals affected with GLI3-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 683 of the GLI3 protein (p.Thr683Ile).
CeGaT Center for Human Genetics Tuebingen	RCV004584861	SCV005075265	uncertain significance	not provided	2024-06-01	criteria provided, single submitter	clinical testing	GLI3: PM2