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

gnomAD frequency: 0.00001  dbSNP: rs777219451

Total submissions: 8

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.
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV001007785	SCV001167470	likely pathogenic	Autosomal recessive multiple pterygium syndrome		no assertion criteria provided	research