Submissions for variant NM_005199.5(CHRNG):c.401_402del (p.Pro134fs)

gnomAD frequency: 0.00011  dbSNP: rs747067203

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000486079	SCV000566548	pathogenic	not provided	2022-11-18	criteria provided, single submitter	clinical testing	Frameshift 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 a significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 34440395, 27245440, 31589614, 16826531)
Molecular Diagnostics Lab, Nemours Children's Health, Delaware	RCV000498334	SCV000590869	pathogenic	Autosomal recessive multiple pterygium syndrome	2016-01-04	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000498334	SCV000807223	pathogenic	Autosomal recessive multiple pterygium syndrome	2023-04-15	criteria provided, single submitter	clinical testing
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	RCV000498334	SCV000996182	pathogenic	Autosomal recessive multiple pterygium syndrome	2018-08-09	criteria provided, single submitter	clinical testing	This frameshifting variant in exon 5 of 12 introduces a premature stop codon and is therefore predicted to result in loss of normal protein function. This variant has been previously reported as a homozygous change in patients with Escobar Variant Multiple Pterygium Syndrome (EVMPS) (PMID: 16826531, 27245440). This alteration is present in the gnomAD population database at a frequency of 0.0079% (22/277144) and thus is presumed to be rare. Based on the available evidence, the c.401_402delCT (p.Pro134ArgfsTer43) variant is classified as pathogenic.
Ambry Genetics	RCV001266730	SCV001444907	pathogenic	Inborn genetic diseases	2019-09-12	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002496856	SCV002813805	pathogenic	Autosomal recessive multiple pterygium syndrome; Lethal multiple pterygium syndrome	2021-10-29	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003333071	SCV004041517	pathogenic	Lethal multiple pterygium syndrome	2023-04-10	criteria provided, single submitter	clinical testing
Invitae	RCV000486079	SCV004449879	pathogenic	not provided	2023-09-24	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: 419026). This variant is also known as p.Pro134fs43Ter. This premature translational stop signal has been observed in individual(s) with multiple pterygium syndrome (PMID: 16826531, 27245440). This variant is present in population databases (rs747067203, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Pro134Argfs*43) in the CHRNG gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CHRNG are known to be pathogenic (PMID: 16826520).