ClinVar Miner

Submissions for variant NM_024577.3(SH3TC2):c.751C>T (p.Pro251Ser) (rs144963732)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Praxis fuer Humangenetik Tuebingen RCV000416281 SCV000493515 uncertain significance not provided 2016-07-01 criteria provided, single submitter clinical testing
GeneDx RCV000416281 SCV000536098 uncertain significance not provided 2018-06-21 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the SH3TC2 gene. The P251S variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The P251S variant is observed in 17/66,674 (0.03%) alleles from individuals of European background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The P251S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000654078 SCV000775968 likely benign Charcot-Marie-Tooth disease type 4 2019-12-27 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000416281 SCV000886107 uncertain significance not provided 2018-01-03 criteria provided, single submitter clinical testing The SH3TC2 c.751C>T; p.Pro251Ser variant (rs144963732), to our knowledge, is not reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is listed in the genome Aggregation Database (gnomAD) with a non-Finnish European population frequency of 0.04% (identified on 48 out of 126,674 chromosomes). The proline at position 251 is highly conserved, considering 8 species, and computational analyses of the effects of the p.Pro251Ser variant on protein structure and function make conflicting predictions (SIFT: tolerated, MutationTaster: disease causing, PolyPhen-2: benign). Based on all available evidence, the clinical significance of the p.Pro251Ser variant cannot be determined with certainty.
Illumina Clinical Services Laboratory,Illumina RCV001153291 SCV001314570 uncertain significance 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, 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 RCV001153292 SCV001314571 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.
Molecular Genetics Laboratory,London Health Sciences Centre RCV001173823 SCV001336937 uncertain significance Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing

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