Submissions for variant NM_015506.3(MMACHC):c.848del (p.Ter283TyrextTer?)

dbSNP: rs1553163024

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000666710	SCV000791053	uncertain significance	Cobalamin C disease	2017-04-24	criteria provided, single submitter	clinical testing
Neuberg Supratech Reference Laboratories Pvt Ltd, Neuberg Centre for Genomic Medicine	RCV000666710	SCV004176605	uncertain significance	Cobalamin C disease	2023-03-01	criteria provided, single submitter	clinical testing	The frame shift c.848del (p.Ter283TyrfsTer8) variant in MMACHC gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Ter283TyrfsTer8 variant has allele frequency 0.0004% in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant has been reported to the ClinVar database as Uncertain Significance. Frame shift change, the sequence of a stop codon is changed to specify an amino acid Tyrosine instead and translation will continue until another stop codon is found at position Ter8. Loss of function variants have been previously reported to be disease causing. However, since this variant is present in the last exon, functional studies will be required to prove protein truncation to prove protein truncation. Hence for these reasons, this variant has been classified as uncertain significance (VUS).