ClinVar Miner

Submissions for variant NM_000193.4(SHH):c.1147G>A (p.Ala383Thr)

gnomAD frequency: 0.00001  dbSNP: rs137853341
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000009436 SCV000784568 uncertain significance Holoprosencephaly 3 2018-03-05 criteria provided, single submitter clinical testing
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000662212 SCV000784569 uncertain significance Schizencephaly 2018-03-05 criteria provided, single submitter clinical testing
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000662213 SCV000784570 uncertain significance Microphthalmia, isolated, with coloboma 5 2018-03-05 criteria provided, single submitter clinical testing
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000662214 SCV000784571 uncertain significance Solitary median maxillary central incisor syndrome 2018-03-05 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV000662212 SCV001367474 uncertain significance Schizencephaly 2020-01-29 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,PP3.
Labcorp Genetics (formerly Invitae), Labcorp RCV000009436 SCV003524407 uncertain significance Holoprosencephaly 3 2022-09-14 criteria provided, single submitter clinical testing Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on SHH function (PMID: 15292211, 32939873). 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 not expected to disrupt SHH protein function. This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 383 of the SHH protein (p.Ala383Thr). This variant is present in population databases (rs137853341, gnomAD no frequency). This missense change has been observed in individual(s) with holoprosencephaly (PMID: 9302262). This variant is also known as Ala384Thr. ClinVar contains an entry for this variant (Variation ID: 8886).
Revvity Omics, Revvity RCV003137506 SCV003820001 uncertain significance not provided 2019-12-18 criteria provided, single submitter clinical testing
OMIM RCV000009436 SCV000029654 pathogenic Holoprosencephaly 3 1997-10-01 no assertion criteria provided literature only
GeneReviews RCV000009436 SCV000087133 pathologic Holoprosencephaly 3 2013-08-29 no assertion criteria provided curation Converted during submission to Pathogenic.

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