Submissions for variant NM_005334.3(HCFC1):c.4619C>T (p.Thr1540Ile)

gnomAD frequency: 0.00002  dbSNP: rs781788935

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000766506	SCV000574015	uncertain significance	not provided	2017-03-22	criteria provided, single submitter	clinical testing	The T1540I variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The T1540I variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The T1540I variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is not conserved, and in silico analysis predicts this variant likely does not alter the protein structure/function. In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Genetic Services Laboratory, University of Chicago	RCV000482310	SCV000595110	uncertain significance	not specified	2016-07-28	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002526976	SCV003277836	likely benign	Methylmalonic acidemia with homocystinuria, type cblX	2023-11-15	criteria provided, single submitter	clinical testing