Submissions for variant NM_001267550.2(TTN):c.95245G>A (p.Glu31749Lys)

gnomAD frequency: 0.00013  dbSNP: rs139542862

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000176957	SCV000228743	uncertain significance	not provided	2017-02-23	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000251152	SCV000318235	uncertain significance	Cardiovascular phenotype	2013-02-18	criteria provided, single submitter	clinical testing	​The p.E29181K variant (also known as c.87541G>A) is located in coding exon 291 of the TTN gene. This alteration results from a G to A substitution at nucleotide position 87541. The glutamate at codon 29181 is replaced by lysine, an amino acid with similar properties. This variant was observed in conjunction with a pathogenic PKP2 mutation in a proband tested by our laboratory who is affected with ADHD, sudden cardiac arrest and syncope. This variant was previously reported in the SNPDatabase as rs139542862. Based on data from the NHLBI Exome Sequencing Project (ESP), the A-allele has an overall frequency of approximately 0.01% (1/12,398), having been observed in 0.02% (1/4038) of African American alleles and in 0% (0/8360) of European American alleles studied. Based on data from the 1000 Genomes Project, the A-allele has an overall frequency of approximately 0.05% (1/2184). The highest observed frequency was 1 of 194 (0.52%) Luhya West African chromosomes. Based on protein sequence alignment, this amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be probably damaging by PolyPhen in silico analysis. Since supporting evidence is limited at this time, the clinical significance of p.E29181K remains unclear.
Invitae	RCV000540643	SCV000643936	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2017-07-27	criteria provided, single submitter	clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000852489	SCV000995185	uncertain significance	Ventricular tachycardia	2017-09-21	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002492767	SCV002776936	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J; Tibial muscular dystrophy; Myopathy, myofibrillar, 9, with early respiratory failure; Early-onset myopathy with fatal cardiomyopathy; Hypertrophic cardiomyopathy 9	2021-07-01	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000176957	SCV003822976	uncertain significance	not provided	2019-04-18	criteria provided, single submitter	clinical testing
GeneDx	RCV000176957	SCV004023447	uncertain significance	not provided	2023-08-04	criteria provided, single submitter	clinical testing	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: 24636144)
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000176957	SCV001956461	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000176957	SCV001964868	uncertain significance	not provided		no assertion criteria provided	clinical testing