ClinVar Miner

Submissions for variant NM_000020.2(ACVRL1):c.1348A>G (p.Thr450Ala) (rs146206499)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000413333 SCV000492219 uncertain significance not specified 2016-11-29 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the ACVRL1 gene. The T450A variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The T450A 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 where only amino acids with similar properties to Threonine are tolerated across species. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Furthermore, the Exome Aggregation Consortium (ExAC) reports T450A was observed in 30/66,722 (0.05%) alleles from individuals of Non-Finnish European background.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign.
Invitae RCV000863196 SCV001003815 benign Telangiectasia, hereditary hemorrhagic, type 2 2020-10-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000863196 SCV001272393 likely benign Telangiectasia, hereditary hemorrhagic, type 2 2018-01-12 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.

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