ClinVar Miner

Submissions for variant NM_001021.6(RPS17):c.1A>G (p.Met1Val)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002417107 SCV002724200 pathogenic Diamond-Blackfan anemia 2015-03-25 criteria provided, single submitter clinical testing The p.M1? pathogenic mutation (also known as c.1A>G), located in coding exon 1 of the RPS17 gene, results from an A to G substitution at nucleotide position 1. This alters the methionine residue at the initiation codon. This mutation has been described to occur de novo in an infant with a clinical diagnosis of Diamond Blackfan Anemia (Song MJ, Pediatr Blood Cancer 2010 Apr; 54(4):629-31). In addition to the clinical data presented in the literature, sequence variations that modify the initiation codon (ATG) are expected to result in either loss of translation initiation or N-terminal truncation, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).
Genetic Services Laboratory, University of Chicago RCV003151406 SCV003839994 likely pathogenic not provided 2022-02-25 no assertion criteria provided clinical testing DNA sequence analysis of the RPS17 gene demonstrated a sequence change, c.1A>G, in exon 1 that impacts the initiator methionine of the RPS17 mRNA. This sequence change may result in an absent or abnormal transcript. This sequence change has been reported in an individual with a diagnosis of Diamond-Blackfan anemia and it was confirmed to be de novo (PMID: 19953637). Additionally, a different sequence change also impacting the initiation codon, c.2T>G, was identified as a de novo variant in a patient with Diamond-Blackfan anemia presenting as macrocytic anemia with increased activity of erythrocyte adenosine deaminase, short stature, facial dysmorphism, and a flat thenar eminence (PMID: 17647292). This sequence change has not been described in population databases such as ExAC and gnomAD. Based on these evidences, this sequence change is likely pathogenic, however functional studies have not been performed to prove this conclusively.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.