TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33755	101488;101489;101490	chr2:178535352;178535351;178535350	chr2:179400079;179400078;179400077
N2AB	32114	96565;96566;96567	chr2:178535352;178535351;178535350	chr2:179400079;179400078;179400077
N2A	31187	93784;93785;93786	chr2:178535352;178535351;178535350	chr2:179400079;179400078;179400077
N2B	24690	74293;74294;74295	chr2:178535352;178535351;178535350	chr2:179400079;179400078;179400077
Novex-1	24815	74668;74669;74670	chr2:178535352;178535351;178535350	chr2:179400079;179400078;179400077
Novex-2	24882	74869;74870;74871	chr2:178535352;178535351;178535350	chr2:179400079;179400078;179400077
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: Fn3-132
• Domain position: 67
• Structural Position: 100
• Q(SASA): 0.21
• 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/E	None	None	0.997	N	0.702	0.402	0.268660756437	gnomAD-4.0.0	1.59111E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43275E-05	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	0.8098	likely_pathogenic	0.8131	pathogenic	-0.037	Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
K/C	0.9242	likely_pathogenic	0.9232	pathogenic	-0.203	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
K/D	0.886	likely_pathogenic	0.8904	pathogenic	0.219	Stabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
K/E	0.6494	likely_pathogenic	0.6287	pathogenic	0.211	Stabilizing	0.997	D	0.702	prob.neutral	N	0.46385767	None	None	N
K/F	0.9716	likely_pathogenic	0.9721	pathogenic	-0.392	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
K/G	0.6309	likely_pathogenic	0.6513	pathogenic	-0.199	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
K/H	0.659	likely_pathogenic	0.6767	pathogenic	-0.576	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
K/I	0.9261	likely_pathogenic	0.9269	pathogenic	0.305	Stabilizing	0.992	D	0.781	deleterious	N	0.483320974	None	None	N
K/L	0.8153	likely_pathogenic	0.8243	pathogenic	0.305	Stabilizing	0.994	D	0.726	prob.delet.	None	None	None	None	N
K/M	0.7222	likely_pathogenic	0.7112	pathogenic	0.235	Stabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
K/N	0.7215	likely_pathogenic	0.7274	pathogenic	0.295	Stabilizing	1.0	D	0.802	deleterious	N	0.436940428	None	None	N
K/P	0.9604	likely_pathogenic	0.9669	pathogenic	0.218	Stabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
K/Q	0.3795	ambiguous	0.3754	ambiguous	0.099	Stabilizing	0.998	D	0.795	deleterious	N	0.496162089	None	None	N
K/R	0.1227	likely_benign	0.1226	benign	0.012	Stabilizing	0.996	D	0.635	neutral	N	0.51474785	None	None	N
K/S	0.8019	likely_pathogenic	0.82	pathogenic	-0.217	Destabilizing	0.999	D	0.762	deleterious	None	None	None	None	N
K/T	0.6861	likely_pathogenic	0.7014	pathogenic	-0.083	Destabilizing	0.999	D	0.751	deleterious	N	0.503877496	None	None	N
K/V	0.8866	likely_pathogenic	0.8883	pathogenic	0.218	Stabilizing	0.995	D	0.765	deleterious	None	None	None	None	N
K/W	0.9737	likely_pathogenic	0.9738	pathogenic	-0.407	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
K/Y	0.9231	likely_pathogenic	0.9197	pathogenic	-0.028	Destabilizing	0.999	D	0.771	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.