Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000179903 | SCV000232221 | uncertain significance | not provided | 2015-05-18 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001215112 | SCV001386836 | uncertain significance | Holoprosencephaly 9; Postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome | 2024-01-22 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 374 of the GLI2 protein (p.Arg374His). This variant is present in population databases (rs370220133, gnomAD 0.007%). This missense change has been observed in individual(s) with unilateral cleft lip and cleft palate (PMID: 16327884). This variant is also known as R46H. ClinVar contains an entry for this variant (Variation ID: 198529). 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 GLI2 protein function with a positive 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. |
ARUP Laboratories, |
RCV000179903 | SCV002049499 | uncertain significance | not provided | 2020-12-14 | criteria provided, single submitter | clinical testing | The GLI2 c.1121G>A; p.Arg374His (rs370220133) variant, also published as R46H, has been reported in an individual with unilateral cleft lip and palate (Vieira 2005). The variant is described in the ClinVar database (Variation ID: 198529) and is found in the general population with an overall allele frequency of 0.005% (13/282,704 alleles). The arginine at codon 374 is highly conserved, but computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.438). Due to limited information, the clinical significance of the p.Arg374His variant is uncertain at this time. References: Vieira AR et al. Medical sequencing of candidate genes for nonsyndromic cleft lip and palate. PLoS Genet. 2005 Dec;1(6):e64. |