ClinVar Miner

Submissions for variant NM_001303256.3(MORC2):c.839C>T (p.Thr280Met)

gnomAD frequency: 0.00002  dbSNP: rs764379949
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000652691 SCV000774562 uncertain significance Charcot-Marie-Tooth disease axonal type 2Z 2024-01-24 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 280 of the MORC2 protein (p.Thr280Met). This variant is present in population databases (rs764379949, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with MORC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 542290). 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 MORC2 protein function with a positive predictive value of 95%. 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 RCV002440368 SCV002677929 uncertain significance Inborn genetic diseases 2022-03-24 criteria provided, single submitter clinical testing The p.T280M variant (also known as c.839C>T), located in coding exon 10 of the MORC2 gene, results from a C to T substitution at nucleotide position 839. The threonine at codon 280 is replaced by methionine, an amino acid with similar properties. This amino acid position is well conserved in available 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.
Institute of Human Genetics, University Hospital Muenster RCV003128415 SCV003804871 uncertain significance See cases 2022-12-08 criteria provided, single submitter clinical testing ACMG categories: PM1

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