TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29476	88651;88652;88653	chr2:178555033;178555032;178555031	chr2:179419760;179419759;179419758
N2AB	27835	83728;83729;83730	chr2:178555033;178555032;178555031	chr2:179419760;179419759;179419758
N2A	26908	80947;80948;80949	chr2:178555033;178555032;178555031	chr2:179419760;179419759;179419758
N2B	20411	61456;61457;61458	chr2:178555033;178555032;178555031	chr2:179419760;179419759;179419758
Novex-1	20536	61831;61832;61833	chr2:178555033;178555032;178555031	chr2:179419760;179419759;179419758
Novex-2	20603	62032;62033;62034	chr2:178555033;178555032;178555031	chr2:179419760;179419759;179419758
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-146
• Domain position: 33
• Structural Position: 50
• Q(SASA): 0.2931
• Predicted PPI site: N

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
K/R	None	None	0.235	N	0.355	0.2	0.202949470691	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	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
K/A	0.9249	likely_pathogenic	0.8924	pathogenic	-0.912	Destabilizing	0.983	D	0.546	neutral	None	None	None	None	N
K/C	0.8415	likely_pathogenic	0.8249	pathogenic	-0.917	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
K/D	0.9898	likely_pathogenic	0.9861	pathogenic	-0.206	Destabilizing	0.998	D	0.709	prob.delet.	None	None	None	None	N
K/E	0.8176	likely_pathogenic	0.7607	pathogenic	-0.067	Destabilizing	0.977	D	0.509	neutral	N	0.511345822	None	None	N
K/F	0.9536	likely_pathogenic	0.9475	pathogenic	-0.643	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
K/G	0.963	likely_pathogenic	0.9508	pathogenic	-1.293	Destabilizing	0.998	D	0.672	neutral	None	None	None	None	N
K/H	0.5727	likely_pathogenic	0.581	pathogenic	-1.661	Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	N
K/I	0.7946	likely_pathogenic	0.7356	pathogenic	0.091	Stabilizing	0.997	D	0.801	deleterious	N	0.510078374	None	None	N
K/L	0.7701	likely_pathogenic	0.7229	pathogenic	0.091	Stabilizing	0.995	D	0.672	neutral	None	None	None	None	N
K/M	0.6532	likely_pathogenic	0.5913	pathogenic	0.043	Stabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
K/N	0.9595	likely_pathogenic	0.9479	pathogenic	-0.644	Destabilizing	0.993	D	0.641	neutral	N	0.511092332	None	None	N
K/P	0.9966	likely_pathogenic	0.9947	pathogenic	-0.215	Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	N
K/Q	0.4257	ambiguous	0.3806	ambiguous	-0.705	Destabilizing	0.993	D	0.619	neutral	N	0.510585353	None	None	N
K/R	0.0892	likely_benign	0.0893	benign	-0.694	Destabilizing	0.235	N	0.355	neutral	N	0.500868902	None	None	N
K/S	0.9541	likely_pathogenic	0.9366	pathogenic	-1.409	Destabilizing	0.983	D	0.567	neutral	None	None	None	None	N
K/T	0.839	likely_pathogenic	0.7908	pathogenic	-1.047	Destabilizing	0.997	D	0.67	neutral	N	0.499482538	None	None	N
K/V	0.7735	likely_pathogenic	0.7153	pathogenic	-0.215	Destabilizing	0.998	D	0.721	prob.delet.	None	None	None	None	N
K/W	0.9192	likely_pathogenic	0.9143	pathogenic	-0.475	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
K/Y	0.8716	likely_pathogenic	0.8723	pathogenic	-0.16	Destabilizing	0.999	D	0.785	deleterious	None	None	None	None	N

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.