Submissions for variant NM_005334.3(HCFC1):c.3845C>T (p.Ser1282Leu)

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	RCV003317878	SCV004021013	uncertain significance	not specified	2023-06-13	criteria provided, single submitter	clinical testing	Variant summary: HCFC1 c.3845C>T (p.Ser1282Leu) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 3.9e-05 in 180301 control chromosomes in GnomAD. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.3845C>T has been reported in a male individual affected with intellectual developmental disorder and epilepsy, but no further clinical information has been provided to establish the diagnosis of Methylmalonic Acidemia With Homocystinuria (Guo_2021). 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 publication have been ascertained in the context of this evaluation (PMID: 33880059). 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 uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003638937	SCV004533567	benign	Methylmalonic acidemia with homocystinuria, type cblX	2024-02-12	criteria provided, single submitter	clinical testing