Submissions for variant NM_144670.6(A2ML1):c.2006C>T (p.Thr669Met)

gnomAD frequency: 0.00001  dbSNP: rs745912214

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001730434	SCV003267261	uncertain significance	not provided	2024-04-29	criteria provided, single submitter	clinical testing	This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 669 of the A2ML1 protein (p.Thr669Met). This variant is present in population databases (rs745912214, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with A2ML1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1299983). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001730434	SCV001979656	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001730434	SCV001980029	likely benign	not provided		no assertion criteria provided	clinical testing