ClinVar Miner

Submissions for variant NM_000020.2(ACVRL1):c.154A>G (p.Thr52Ala) (rs1131691346)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000493775 SCV000581923 likely pathogenic not provided 2015-08-19 criteria provided, single submitter clinical testing The T52A variant has been reported in a patient with telangiectasias and AVMs, and was absent from at least 200 control individuals (Bossler et al., 2006). The T52A variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The T52A 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. Functional studies demonstrate that the T52 residue plays an important role in stabilizing the protein structure (Scotti et al., 2011; Townson et al., 2012). Finally, another variant at the same residue (T52P) was reported in an individual with a clinical diagnosis of HHT (Nishimoto et al., 2014), and variants in nearby residues (G48E, W50G, W50C, C51Y) have been reported in HGMD in association with HHT (Stenson P et al., 2014), supporting the functional importance of this residue and this region of the protein.Therefore, this variant is a strong candidate for a pathogenic variant, however the possibility that it is a benign variant cannot be excluded

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