Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000815446 | SCV000955899 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2Z | 2023-01-27 | criteria provided, single submitter | clinical testing | 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 MORC2 protein function. ClinVar contains an entry for this variant (Variation ID: 658592). This variant has not been reported in the literature in individuals affected with MORC2-related conditions. This variant is present in population databases (rs746418433, gnomAD 0.009%). This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 748 of the MORC2 protein (p.Val748Ala). 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. |
| Ambry Genetics | RCV002422822 | SCV002724990 | uncertain significance | Inborn genetic diseases | 2020-06-22 | criteria provided, single submitter | clinical testing | The p.V748A variant (also known as c.2243T>C), located in coding exon 20 of the MORC2 gene, results from a T to C substitution at nucleotide position 2243. The valine at codon 748 is replaced by alanine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and alanine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003387935 | SCV004100145 | uncertain significance | not specified | 2023-09-26 | criteria provided, single submitter | clinical testing | Variant summary: MORC2 c.2243T>C (p.Val748Ala) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 251408 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2243T>C in individuals affected with Developmental Delay, Impaired Growth, Dysmorphic Facies, And Axonal Neuropathy and no experimental evidence demonstrating its impact on protein function have been reported. Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Both submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |