Submissions for variant NM_018389.5(SLC35C1):c.942C>G (p.Tyr314Ter)

gnomAD frequency: 0.00001  dbSNP: rs766512058

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000598876	SCV000710600	likely pathogenic	not provided	2018-02-09	criteria provided, single submitter	clinical testing	The Y314X variant in the SLC35C1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant is predicted to cause loss of normal protein function through protein truncation. The Y314X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). We interpret Y314X as a likely pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003611523	SCV004375980	pathogenic	Leukocyte adhesion deficiency type II	2022-11-01	criteria provided, single submitter	clinical testing	This variant disrupts a region of the SLC35C1 protein in which other variant(s) (p.Lys322*) have been determined to be pathogenic (PMID: 16455955). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 504285). This premature translational stop signal has been observed in individual(s) with congenital disorders of glycosylation (PMID: 33413482). This variant is present in population databases (rs766512058, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Tyr314*) in the SLC35C1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 51 amino acid(s) of the SLC35C1 protein.