Submissions for variant NM_139343.3(BIN1):c.696C>A (p.Asn232Lys)

gnomAD frequency: 0.00034  dbSNP: rs143820618

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000514580	SCV000329112	uncertain significance	not provided	2022-03-29	criteria provided, single submitter	clinical testing	Reported in an individual with familial congenital heart disease, however, further clinical information was not provided and the individual may have harbored additional variants in other genes (Alankarage et al., 2019); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 30293987)
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000514580	SCV000609730	uncertain significance	not provided	2017-05-19	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000529083	SCV000634518	uncertain significance	Myopathy, centronuclear, 2	2023-11-03	criteria provided, single submitter	clinical testing	This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 232 of the BIN1 protein (p.Asn232Lys). This variant is present in population databases (rs143820618, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with BIN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 158016). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics	RCV000529083	SCV000896804	uncertain significance	Myopathy, centronuclear, 2	2018-10-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000529083	SCV001291619	uncertain significance	Myopathy, centronuclear, 2	2018-01-13	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Breda Genetics srl	RCV000529083	SCV002583843	uncertain significance	Myopathy, centronuclear, 2	2022-05-17	criteria provided, single submitter	clinical testing	Based on allele frequency, in-silico prediction scores and a certain overlap with the clinical phenotype, we interpreted this variant at least as of uncertain significance. The lack of one or more of the following features has discouraged further investigations: lack of a possible second hit in autosomal recessive conditions, presence of healthy controls in databases for autosomal dominant conditions, presence of unmatching cardinal clinical features in the patient or in the known gene-disease association, and/or variant type outside the known gene mutational spectrum.
Revvity Omics, Revvity	RCV000529083	SCV003829886	uncertain significance	Myopathy, centronuclear, 2	2019-06-27	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000514580	SCV004224948	uncertain significance	not provided	2023-04-12	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000145344	SCV000192423	likely benign	not specified		no assertion criteria provided	clinical testing
GenomeConnect - Invitae Patient Insights Network	RCV000529083	SCV004228613	not provided	Myopathy, centronuclear, 2		no assertion provided	phenotyping only	Variant interpreted as Uncertain significance and reported on 05-24-2021 by Lab 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.