Submissions for variant NM_173660.5(DOK7):c.1378dup (p.Gln460fs)

dbSNP: rs606231133

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000810664	SCV000950890	pathogenic	Fetal akinesia deformation sequence 1; Congenital myasthenic syndrome 10	2024-12-03	criteria provided, single submitter	clinical testing	This sequence change results in a frameshift in the DOK7 gene (p.Gln460Profs*59). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 45 amino acid(s) of the DOK7 protein and extend the protein by 13 additional amino acid residues. This variant is present in population databases (rs747302811, gnomAD 0.03%). This frameshift has been observed in individuals with congenital myasthenic syndrome (PMID: 16917026, 18626973). ClinVar contains an entry for this variant (Variation ID: 1282). Algorithms developed to predict the effect of variants on gene product structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this frameshift affects DOK7 function (PMID: 18626973). This variant results in an extension of the DOK7 protein. Other variant(s) that result in a similarly extended protein product (p.Pro504Serfs*15) have been observed in individuals with DOK7-related disease (PMID: 16917026). This suggests that these extensions may be clinically significant. For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity	RCV001781162	SCV002021746	pathogenic	not provided	2021-12-27	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001781162	SCV002062537	pathogenic	not provided	2023-01-01	criteria provided, single submitter	clinical testing	DOK7: PP1:Strong, PM2, PVS1:Moderate, PP4, PS3:Supporting
Institute for Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin	RCV000001345	SCV002578150	likely pathogenic	Congenital myasthenic syndrome 10	2022-09-27	criteria provided, single submitter	clinical testing
Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences	RCV003232983	SCV002760188	likely pathogenic	Fetal akinesia deformation sequence 3	2022-12-12	criteria provided, single submitter	research
Baylor Genetics	RCV003232983	SCV004194012	pathogenic	Fetal akinesia deformation sequence 3	2024-03-18	criteria provided, single submitter	clinical testing
GeneDx	RCV001781162	SCV005325053	likely pathogenic	not provided	2024-03-07	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein elongation, as the last 45 amino acids are replaced with 58 different amino acids, and other loss-of-function variants have been reported downstream in HGMD; This variant is associated with the following publications: (PMID: 32360404, Jadhav2019[casereport], 34418069, 33820833, 36308527, 28508085, 16917026, 18626973)
Mayo Clinic Laboratories, Mayo Clinic	RCV001781162	SCV005413636	pathogenic	not provided	2024-08-13	criteria provided, single submitter	clinical testing	PM2, PM3_strong, PS4_moderate, PVS1_strong
Institute of Human Genetics, University Hospital Muenster	RCV004797747	SCV005419364	pathogenic	See cases	2024-09-05	criteria provided, single submitter	clinical testing	ACMG categories: PVS1_mod,PS3,PS4,PM2_sup
OMIM	RCV000001345	SCV000021495	pathogenic	Congenital myasthenic syndrome 10	2008-07-01	no assertion criteria provided	literature only