TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14832	44719;44720;44721	chr2:178625327;178625326;178625325	chr2:179490054;179490053;179490052
N2AB	13191	39796;39797;39798	chr2:178625327;178625326;178625325	chr2:179490054;179490053;179490052
N2A	12264	37015;37016;37017	chr2:178625327;178625326;178625325	chr2:179490054;179490053;179490052
N2B	5767	17524;17525;17526	chr2:178625327;178625326;178625325	chr2:179490054;179490053;179490052
Novex-1	5892	17899;17900;17901	chr2:178625327;178625326;178625325	chr2:179490054;179490053;179490052
Novex-2	5959	18100;18101;18102	chr2:178625327;178625326;178625325	chr2:179490054;179490053;179490052
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-99
• Domain position: 68
• Structural Position: 153
• Q(SASA): 0.3527
• 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
E/G	rs1354845947	None	0.994	D	0.647	0.56	0.582764979894	gnomAD-4.0.0	1.61298E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.46374E-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
E/A	0.1644	likely_benign	0.1567	benign	-0.409	Destabilizing	0.989	D	0.591	neutral	D	0.55728278	None	None	N
E/C	0.8964	likely_pathogenic	0.8821	pathogenic	-0.285	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
E/D	0.1846	likely_benign	0.1793	benign	-1.207	Destabilizing	0.217	N	0.323	neutral	N	0.510093082	None	None	N
E/F	0.7876	likely_pathogenic	0.7592	pathogenic	-0.492	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
E/G	0.2747	likely_benign	0.2664	benign	-0.73	Destabilizing	0.994	D	0.647	neutral	D	0.674023997	None	None	N
E/H	0.5668	likely_pathogenic	0.521	ambiguous	-1.003	Destabilizing	1.0	D	0.649	neutral	None	None	None	None	N
E/I	0.3218	likely_benign	0.3022	benign	0.44	Stabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
E/K	0.1475	likely_benign	0.1407	benign	-0.7	Destabilizing	0.978	D	0.527	neutral	N	0.506578377	None	None	N
E/L	0.405	ambiguous	0.3724	ambiguous	0.44	Stabilizing	0.998	D	0.763	deleterious	None	None	None	None	N
E/M	0.4263	ambiguous	0.4046	ambiguous	0.872	Stabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
E/N	0.3169	likely_benign	0.3093	benign	-0.891	Destabilizing	0.998	D	0.624	neutral	None	None	None	None	N
E/P	0.5435	ambiguous	0.5134	ambiguous	0.18	Stabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
E/Q	0.156	likely_benign	0.1495	benign	-0.771	Destabilizing	0.889	D	0.275	neutral	N	0.506294339	None	None	N
E/R	0.2882	likely_benign	0.2556	benign	-0.675	Destabilizing	0.998	D	0.644	neutral	None	None	None	None	N
E/S	0.2624	likely_benign	0.2493	benign	-1.186	Destabilizing	0.992	D	0.552	neutral	None	None	None	None	N
E/T	0.2386	likely_benign	0.2277	benign	-0.936	Destabilizing	0.999	D	0.71	prob.delet.	None	None	None	None	N
E/V	0.1973	likely_benign	0.1849	benign	0.18	Stabilizing	0.998	D	0.753	deleterious	N	0.51283326	None	None	N
E/W	0.9293	likely_pathogenic	0.9122	pathogenic	-0.578	Destabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	N
E/Y	0.7178	likely_pathogenic	0.6832	pathogenic	-0.34	Destabilizing	1.0	D	0.749	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.