ClinVar Miner

Submissions for variant NM_000401.3(EXT2):c.2015C>T (p.Thr672Met) (rs138722406)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mayo Clinic Laboratories, Mayo Clinic RCV000660594 SCV000782708 uncertain significance Seizures, scoliosis, and macrocephaly syndrome 2017-07-24 criteria provided, single submitter clinical testing
Invitae RCV000806392 SCV000946387 uncertain significance Multiple exostoses type 2 2018-11-16 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 639 of the EXT2 protein (p.Thr639Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs138722406, ExAC 0.01%). This variant has not been reported in the literature in individuals with EXT2-related disease. ClinVar contains an entry for this variant (Variation ID: 134205). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Illumina Clinical Services Laboratory,Illumina RCV000806392 SCV001259400 likely benign Multiple exostoses type 2 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.
ITMI RCV000120878 SCV000085046 not provided not specified 2013-09-19 no assertion provided reference population
OMIM RCV000660594 SCV000930614 pathogenic Seizures, scoliosis, and macrocephaly syndrome 2019-08-02 no assertion criteria provided literature only

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