Submissions for variant NM_022489.4(INF2):c.3103G>A (p.Gly1035Ser)

gnomAD frequency: 0.00019  dbSNP: rs368995122

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000757410	SCV000529456	likely benign	not provided	2019-09-16	criteria provided, single submitter	clinical testing
Invitae	RCV000525037	SCV000652102	likely benign	Focal segmental glomerulosclerosis 5; Charcot-Marie-Tooth disease dominant intermediate E	2024-01-18	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000757410	SCV000885619	uncertain significance	not provided	2018-01-12	criteria provided, single submitter	clinical testing	The INF2 c.3103G>A; p.Gly1035Ser variant (rs368995122), to our knowledge, is not reported in the medical literature nor has it been previously identified by our laboratory. It is listed in the Genome Aggregation Database (gnomAD) browser with an allele frequency of 0.03% in the non-Finnish European population (identified in 33 out of 110,380 chromosomes), and is classified as likely benign/unknown significance in ClinVar (Variant ID: 387417). The glycine at position 1035 is weakly conserved, considering 12 species, and computational analyses of the effects of the p.Gly1035Ser variant on protein structure and function do not predict a deleterious effect (SIFT: tolerated, MutationTaster: polymorphism, PolyPhen-2: benign). Based on the available information, the clinical significance of the p.Gly1035Ser variant cannot be determined with certainty.
Illumina Laboratory Services, Illumina	RCV001113918	SCV001271731	benign	Focal segmental glomerulosclerosis 5	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Ambry Genetics	RCV002323635	SCV002607807	benign	Inborn genetic diseases	2021-06-16	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
CeGaT Center for Human Genetics Tuebingen	RCV000757410	SCV004184431	uncertain significance	not provided	2023-11-01	criteria provided, single submitter	clinical testing	INF2: PM2, BP4
GenomeConnect - Invitae Patient Insights Network	RCV000525037	SCV001749782	not provided	Focal segmental glomerulosclerosis 5; Charcot-Marie-Tooth disease dominant intermediate E		no assertion provided	phenotyping only	Variant interpreted as Uncertain significance and reported on 01-29-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.