ClinVar Miner

Submissions for variant NM_024577.3(SH3TC2):c.3380G>A (p.Arg1127Gln) (rs139192433)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000214292 SCV000279172 uncertain significance not provided 2017-06-22 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the SH3TC2 gene. This variant was observed in the heterozygous state in 3 individuals with symptoms of CMT1 and was described as being a variant of unknown significance (Antoniadi et al., 2015). A missense variant in the same residue (R1127W) has been reported in the Human Gene Mutation Database in association with SH3TC2-related disease (Stenson et al., 2014). The 1000 Genomes Project reports R1127Q was observed in 2/182 (1.1%) alleles from individuals of British background, and the NHLBI Exome Sequencing Project reports R1127Q was observed in 19/8600 (0.2%) alleles from individuals of European background. The R1127Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Additionally, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Illumina Clinical Services Laboratory,Illumina RCV001095006 SCV000454522 uncertain significance Charcot-Marie-Tooth disease, type 4C 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000355518 SCV000454523 likely benign Mononeuropathy of the median nerve, mild 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Invitae RCV000473910 SCV000546363 likely benign Charcot-Marie-Tooth disease type 4 2019-12-31 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000214292 SCV001145612 uncertain significance not provided 2018-11-01 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000214292 SCV001154549 uncertain significance not provided 2020-01-01 criteria provided, single submitter clinical testing
Molecular Genetics Laboratory,London Health Sciences Centre RCV001173826 SCV001336942 uncertain significance Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing

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