Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000009433 | SCV001210478 | likely pathogenic | Holoprosencephaly 3 | 2023-07-19 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 8883). This missense change has been observed in individuals with midline defects (PMID: 9302262, 22897141, 29205322). This variant is present in population databases (rs104894043, gnomAD 0.009%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 226 of the SHH protein (p.Ala226Thr). 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 SHH protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this missense change affects SHH function (PMID: 15292211, 22897141). |
Ce |
RCV001092783 | SCV001249440 | pathogenic | not provided | 2019-08-01 | criteria provided, single submitter | clinical testing | |
Laboratory of Human Genetics, |
RCV001813967 | SCV002060423 | uncertain significance | Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies | 2019-01-16 | criteria provided, single submitter | research | Maternal inheritance. Presence of the variant confirmed by sanger in one sister and absent in the other. SHH pathogenic variants have incomplete penetrance and variable expressivity. Further, the phenotype is not suggestive of variants in this gene. |
OMIM | RCV000009433 | SCV000029651 | pathogenic | Holoprosencephaly 3 | 1997-10-01 | no assertion criteria provided | literature only | |
Gene |
RCV000009433 | SCV000087214 | pathologic | Holoprosencephaly 3 | 2013-08-29 | no assertion criteria provided | curation | Converted during submission to Pathogenic. |