Submissions for variant NM_004211.5(SLC6A5):c.9C>A (p.Cys3Ter)

gnomAD frequency: 0.00002  dbSNP: rs752254977

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000522358	SCV000616880	likely pathogenic	not provided	2022-10-17	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge
Invitae	RCV001857938	SCV002230334	pathogenic	Hyperekplexia 3	2023-11-19	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Cys3*) in the SLC6A5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC6A5 are known to be pathogenic (PMID: 14622583, 16751771, 22700964). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with SLC6A5-related conditions. ClinVar contains an entry for this variant (Variation ID: 449100). For these reasons, this variant has been classified as Pathogenic.
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology	RCV001857938	SCV002575014	likely pathogenic	Hyperekplexia 3	2022-09-26	criteria provided, single submitter	research	PVS1, PM2
Fulgent Genetics, Fulgent Genetics	RCV001857938	SCV002809797	likely pathogenic	Hyperekplexia 3	2021-09-08	criteria provided, single submitter	clinical testing