Submissions for variant NM_004341.5(CAD):c.3775G>A (p.Val1259Met)

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	RCV004766843	SCV005380592	uncertain significance	not specified	2024-08-30	criteria provided, single submitter	clinical testing	Variant summary: CAD c.3775G>A (p.Val1259Met) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251296 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.3775G>A has been reported in the literature in one compound heterozygous individual affected with with global developmental delay, refractory epilepsy, and anemia with anisopoikilocytosis (Zhou_2020). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 32820246, 32117025). No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as uncertain significance.
Juno Genomics, Hangzhou Juno Genomics, Inc	RCV004796887	SCV005418136	likely pathogenic	Developmental and epileptic encephalopathy, 50		criteria provided, single submitter	clinical testing	PM2_Supporting+PP3+PS2_Supporting+PM3+PP4