ClinVar Miner

Submissions for variant NM_144670.6(A2ML1):c.3495C>G (p.Ile1165Met)

gnomAD frequency: 0.00001  dbSNP: rs868320081
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000610364 SCV000721331 likely benign not specified 2017-07-18 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000610364 SCV001370683 uncertain significance not specified 2020-05-18 criteria provided, single submitter clinical testing Variant summary: A2ML1 c.3495C>G (p.Ile1165Met) results in a conservative amino acid change located in the Alpha-macroglobulin-like, TED domain (IPR011626) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 249042 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.3495C>G in individuals affected with Noonan Syndrome And Related Conditions and no experimental evidence demonstrating its impact on protein function have been reported. A ClinVar submitter (evaluation after 2014) cites the variant as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance.
Ambry Genetics RCV003160097 SCV003856918 uncertain significance Inborn genetic diseases 2023-02-26 criteria provided, single submitter clinical testing The p.I1165M variant (also known as c.3495C>G), located in coding exon 28 of the A2ML1 gene, results from a C to G substitution at nucleotide position 3495. The isoleucine at codon 1165 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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