Submissions for variant NM_024757.5(EHMT1):c.2704C>T (p.Arg902Ter)

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Total submissions: 4

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000336966	SCV000330618	pathogenic	not provided	2018-07-10	criteria provided, single submitter	clinical testing	The R902X pathogenic variant in the EHMT1 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 either through protein truncation or nonsense-mediated mRNA decay. The R902X variant is not observed in large population cohorts (Lek et al., 2016). Additionally, the R902X variant has occurred de novo in this individual, as well as in two other unrelated individuals with features consistent with Kleefstra syndrome tested at GeneDx. Therefore, this variant is considered pathogenic.
3billion	RCV001808728	SCV002058486	pathogenic	Kleefstra syndrome 1	2022-01-03	criteria provided, single submitter	clinical testing	Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). It is not observed in the gnomAD v2.1.1 dataset (PM2_M). The variant has been reported to be associated with EHMT1 related disorder (ClinVar ID: VCV000280682). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Laboratory of Human Genetics, Universidade de São Paulo	RCV001808728	SCV002060419	pathogenic	Kleefstra syndrome 1	2019-10-16	criteria provided, single submitter	research	ACMG: PVS1, PS2, PM2, PP3, and PP5
Invitae	RCV001808728	SCV004458735	pathogenic	Kleefstra syndrome 1	2023-04-17	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 280682). This variant has not been reported in the literature in individuals affected with EHMT1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg902*) in the EHMT1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in EHMT1 are known to be pathogenic (PMID: 16826528, 19264732).

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