Submissions for variant NM_024577.4(SH3TC2):c.1342G>C (p.Asp448His)

gnomAD frequency: 0.00001  dbSNP: rs587781252

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000801956	SCV000941762	uncertain significance	Charcot-Marie-Tooth disease type 4	2022-10-13	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 448 of the SH3TC2 protein (p.Asp448His). This variant is present in population databases (rs587781252, gnomAD 0.009%). This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 25025039). ClinVar contains an entry for this variant (Variation ID: 157533). 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. 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.
Mayo Clinic Laboratories, Mayo Clinic	RCV004791277	SCV005411900	uncertain significance	not provided	2023-08-17	criteria provided, single submitter	clinical testing
Dept. of Medical Genetics, Telemark Hospital Trust, Telemark Hospital Trust	RCV000144879	SCV000172151	uncertain significance	Charcot-Marie-Tooth disease	2013-11-01	no assertion criteria provided	research