ClinVar Miner

Submissions for variant NM_024577.4(SH3TC2):c.3736G>A (p.Asp1246Asn)

gnomAD frequency: 0.00004  dbSNP: rs753142542
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV001200174 SCV001371065 uncertain significance not provided 2023-03-01 criteria provided, single submitter clinical testing SH3TC2: PM2, BP4
Invitae RCV001216324 SCV001388115 uncertain significance Charcot-Marie-Tooth disease type 4 2024-01-22 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1246 of the SH3TC2 protein (p.Asp1246Asn). This variant is present in population databases (rs753142542, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with SH3TC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 932396). 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 SH3TC2 protein function with a negative 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 RCV002348645 SCV002622535 uncertain significance Inborn genetic diseases 2020-11-23 criteria provided, single submitter clinical testing The p.D1246N variant (also known as c.3736G>A), located in coding exon 17 of the SH3TC2 gene, results from a G to A substitution at nucleotide position 3736. The aspartic acid at codon 1246 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species; however, asparagine 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.
New York Genome Center RCV003336329 SCV004046497 uncertain significance Charcot-Marie-Tooth disease type 4C; Susceptibility to mononeuropathy of the median nerve, mild 2023-04-10 criteria provided, single submitter clinical testing

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