Submissions for variant NM_001082971.2(DDC):c.1241dup (p.Ser416fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003123405	SCV003800835	likely pathogenic	Deficiency of aromatic-L-amino-acid decarboxylase	2023-01-05	criteria provided, single submitter	clinical testing	Variant summary: DDC c.1241dupA (p.Ser416PhefsX6) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. At least one truncation downstream of this position has been classified as pathogenic in ClinVar. The variant was absent in 251360 control chromosomes (gnomAD). To our knowledge, no occurrence of c.1241dupA in individuals affected with Deficiency Of Aromatic-L-Amino-Acid Decarboxylase and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003123405	SCV004373279	pathogenic	Deficiency of aromatic-L-amino-acid decarboxylase	2022-12-25	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with DDC-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser416Phefs*6) in the DDC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DDC are known to be pathogenic (PMID: 15079002, 24788355).