Submissions for variant NM_005199.5(CHRNG):c.256C>T (p.Arg86Cys)

gnomAD frequency: 0.00001  dbSNP: rs777219451

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Claritas Genomics	RCV000449634	SCV000537827	likely pathogenic	Peripheral neuropathy	2016-08-22	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000762330	SCV000892636	pathogenic	not provided	2018-08-01	criteria provided, single submitter	clinical testing
Clinical Genetics and Genomics, Karolinska University Hospital	RCV000762330	SCV001449542	likely pathogenic	not provided	2019-12-19	criteria provided, single submitter	clinical testing
GeneDx	RCV000762330	SCV003837510	pathogenic	not provided	2023-02-08	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 16826520, 31230720, 30868735, 34426522, 26752647)
Duke University Health System Sequencing Clinic, Duke University Health System	RCV001007785	SCV003918956	likely pathogenic	Autosomal recessive multiple pterygium syndrome	2023-04-20	criteria provided, single submitter	research
Center of Genomic medicine, Geneva, University Hospital of Geneva	RCV001007785	SCV004098980	likely pathogenic	Autosomal recessive multiple pterygium syndrome	2023-01-17	criteria provided, single submitter	clinical testing	The patient harbours this variant in an homozygous state, each copy being inherited form each parent
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003479120	SCV004223810	pathogenic	Lethal multiple pterygium syndrome	2023-11-14	criteria provided, single submitter	clinical testing	Variant summary: CHRNG c.256C>T (p.Arg86Cys) results in a non-conservative amino acid change located in the neurotransmitter-gated ion-channel transmembrane domain (IPR006029) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 248786 control chromosomes (gnomAD). c.256C>T has been reported in the literature as a biallelic genotype in multiple individuals affected with Escobar Syndrome/Lethal Multiple Pterygium Syndrome - CHRNG Related (e.g. Hoffmann_2006, Bayram_2016, Pehlivan_2019). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 16826520, 26752647, 31230720). Six submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV001007785	SCV004807824	pathogenic	Autosomal recessive multiple pterygium syndrome	2024-03-29	criteria provided, single submitter	clinical testing
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV001007785	SCV001167470	likely pathogenic	Autosomal recessive multiple pterygium syndrome		no assertion criteria provided	research