ClinVar Miner

Submissions for variant NM_182894.3(VSX2):c.679C>T (p.Arg227Trp)

gnomAD frequency: 0.00002  dbSNP: rs121912545
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Total submissions: 6
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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 RCV000015988 SCV000845242 uncertain significance Isolated microphthalmia 2 2018-08-07 criteria provided, single submitter clinical testing
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000714543 SCV000845243 uncertain significance Microphthalmia, isolated, with coloboma 3 2018-08-07 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000015988 SCV002247338 pathogenic Isolated microphthalmia 2 2023-01-14 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects VSX2 function (PMID: 23028343). 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 VSX2 protein function. ClinVar contains an entry for this variant (Variation ID: 14862). This missense change has been observed in individuals with microphthalmia (PMID: 15257456, 20414678). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs121912545, gnomAD 0.007%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 227 of the VSX2 protein (p.Arg227Trp).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004586011 SCV005076224 pathogenic VSX2-related Microphthalmia 2024-04-15 criteria provided, single submitter clinical testing Variant summary: VSX2 c.679C>T (p.Arg227Trp) results in a non-conservative amino acid change located in the CVC domain (IPR023339) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 251100 control chromosomes (gnomAD). c.679C>T has been reported in the literature in several homozygous individuals affected with VSX2-related Microphthalmia (Bar-Yosef_2004). These data indicate that the variant is very likely to be associated with disease. The following publication has been ascertained in the context of this evaluation (PMID: 15257456). ClinVar contains an entry for this variant (Variation ID: 14862). Based on the evidence outlined above, the variant was classified as pathogenic.
OMIM RCV000015988 SCV000036255 pathogenic Isolated microphthalmia 2 2004-09-01 no assertion criteria provided literature only
Molecular Genetics Laboratory, Institute for Ophthalmic Research RCV000786019 SCV000924659 pathogenic Microphthalmia; Anophthalmia 2017-12-13 no assertion criteria provided research

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