Submissions for variant NM_002454.3(MTRR):c.1A>G (p.Met1Val)

dbSNP: rs1747827267

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001059702	SCV001224339	likely pathogenic	Methylcobalamin deficiency type cblE	2021-04-09	criteria provided, single submitter	clinical testing	In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Ser454 amino acid residue in MTRR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12971424, 25978498, 22887477). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with MTRR-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change affects the initiator methionine of the MTRR mRNA. The next in-frame methionine is located at codon 542.