TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16970	51133;51134;51135	chr2:178611221;178611220;178611219	chr2:179475948;179475947;179475946
N2AB	15329	46210;46211;46212	chr2:178611221;178611220;178611219	chr2:179475948;179475947;179475946
N2A	14402	43429;43430;43431	chr2:178611221;178611220;178611219	chr2:179475948;179475947;179475946
N2B	7905	23938;23939;23940	chr2:178611221;178611220;178611219	chr2:179475948;179475947;179475946
Novex-1	8030	24313;24314;24315	chr2:178611221;178611220;178611219	chr2:179475948;179475947;179475946
Novex-2	8097	24514;24515;24516	chr2:178611221;178611220;178611219	chr2:179475948;179475947;179475946
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-111
• Domain position: 16
• Structural Position: 25
• Q(SASA): 0.4045
• Predicted PPI site: I

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
E/K	rs1351961700	0.049	0.955	N	0.459	0.259	0.208000267992	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.93E-06	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
E/A	0.324	likely_benign	0.3047	benign	-0.78	Destabilizing	0.977	D	0.556	neutral	N	0.451140341	None	None	I
E/C	0.9144	likely_pathogenic	0.8986	pathogenic	-0.216	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
E/D	0.1899	likely_benign	0.1839	benign	-0.553	Destabilizing	0.977	D	0.394	neutral	N	0.455790457	None	None	I
E/F	0.9094	likely_pathogenic	0.8973	pathogenic	-0.554	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
E/G	0.2451	likely_benign	0.2282	benign	-1.012	Destabilizing	0.993	D	0.668	neutral	N	0.450144372	None	None	I
E/H	0.6575	likely_pathogenic	0.6009	pathogenic	-0.488	Destabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	I
E/I	0.6998	likely_pathogenic	0.6787	pathogenic	-0.184	Destabilizing	0.998	D	0.768	deleterious	None	None	None	None	I
E/K	0.2294	likely_benign	0.2005	benign	0.051	Stabilizing	0.955	D	0.459	neutral	N	0.460284237	None	None	I
E/L	0.6994	likely_pathogenic	0.6593	pathogenic	-0.184	Destabilizing	0.995	D	0.737	prob.delet.	None	None	None	None	I
E/M	0.6697	likely_pathogenic	0.631	pathogenic	0.092	Stabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	I
E/N	0.3106	likely_benign	0.2886	benign	-0.365	Destabilizing	0.995	D	0.7	prob.neutral	None	None	None	None	I
E/P	0.9708	likely_pathogenic	0.959	pathogenic	-0.363	Destabilizing	0.998	D	0.715	prob.delet.	None	None	None	None	I
E/Q	0.1634	likely_benign	0.1481	benign	-0.322	Destabilizing	0.568	D	0.301	neutral	N	0.457218846	None	None	I
E/R	0.3991	ambiguous	0.3524	ambiguous	0.249	Stabilizing	0.99	D	0.703	prob.neutral	None	None	None	None	I
E/S	0.2962	likely_benign	0.2848	benign	-0.536	Destabilizing	0.983	D	0.573	neutral	None	None	None	None	I
E/T	0.4123	ambiguous	0.3879	ambiguous	-0.343	Destabilizing	0.995	D	0.688	prob.neutral	None	None	None	None	I
E/V	0.4756	ambiguous	0.451	ambiguous	-0.363	Destabilizing	0.997	D	0.735	prob.delet.	D	0.576775995	None	None	I
E/W	0.9618	likely_pathogenic	0.9545	pathogenic	-0.318	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	I
E/Y	0.8262	likely_pathogenic	0.8036	pathogenic	-0.301	Destabilizing	0.999	D	0.754	deleterious	None	None	None	None	I

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.