TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22344	67255;67256;67257	chr2:178580349;178580348;178580347	chr2:179445076;179445075;179445074
N2AB	20703	62332;62333;62334	chr2:178580349;178580348;178580347	chr2:179445076;179445075;179445074
N2A	19776	59551;59552;59553	chr2:178580349;178580348;178580347	chr2:179445076;179445075;179445074
N2B	13279	40060;40061;40062	chr2:178580349;178580348;178580347	chr2:179445076;179445075;179445074
Novex-1	13404	40435;40436;40437	chr2:178580349;178580348;178580347	chr2:179445076;179445075;179445074
Novex-2	13471	40636;40637;40638	chr2:178580349;178580348;178580347	chr2:179445076;179445075;179445074
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-126
• Domain position: 80
• Structural Position: 168
• Q(SASA): 0.3699
• 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/D	rs1022112057	None	0.425	N	0.25	0.086	0.33340067248	gnomAD-4.0.0	1.59273E-06	None	None	None	None	I	None	0	0	None	0	2.77624E-05	None	0	0	0	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
E/A	0.1613	likely_benign	0.1531	benign	-0.714	Destabilizing	0.002	N	0.131	neutral	N	0.490079558	None	None	I
E/C	0.8199	likely_pathogenic	0.8178	pathogenic	-0.451	Destabilizing	0.981	D	0.321	neutral	None	None	None	None	I
E/D	0.2079	likely_benign	0.1881	benign	-0.797	Destabilizing	0.425	N	0.25	neutral	N	0.499584476	None	None	I
E/F	0.8797	likely_pathogenic	0.8654	pathogenic	0.032	Stabilizing	0.944	D	0.389	neutral	None	None	None	None	I
E/G	0.2962	likely_benign	0.2793	benign	-1.062	Destabilizing	0.27	N	0.325	neutral	N	0.501322412	None	None	I
E/H	0.6438	likely_pathogenic	0.6158	pathogenic	0.003	Stabilizing	0.981	D	0.293	neutral	None	None	None	None	I
E/I	0.4016	ambiguous	0.3791	ambiguous	0.233	Stabilizing	0.704	D	0.443	neutral	None	None	None	None	I
E/K	0.3914	ambiguous	0.3721	ambiguous	-0.29	Destabilizing	0.425	N	0.251	neutral	N	0.504123504	None	None	I
E/L	0.5951	likely_pathogenic	0.5732	pathogenic	0.233	Stabilizing	0.329	N	0.37	neutral	None	None	None	None	I
E/M	0.487	ambiguous	0.4622	ambiguous	0.46	Stabilizing	0.981	D	0.324	neutral	None	None	None	None	I
E/N	0.3011	likely_benign	0.2744	benign	-0.927	Destabilizing	0.495	N	0.188	neutral	None	None	None	None	I
E/P	0.8959	likely_pathogenic	0.8988	pathogenic	-0.061	Destabilizing	0.828	D	0.329	neutral	None	None	None	None	I
E/Q	0.1605	likely_benign	0.1604	benign	-0.775	Destabilizing	0.784	D	0.228	neutral	N	0.491887712	None	None	I
E/R	0.5555	ambiguous	0.5447	ambiguous	0.088	Stabilizing	0.704	D	0.185	neutral	None	None	None	None	I
E/S	0.1492	likely_benign	0.136	benign	-1.174	Destabilizing	0.004	N	0.122	neutral	None	None	None	None	I
E/T	0.1425	likely_benign	0.1359	benign	-0.873	Destabilizing	0.004	N	0.124	neutral	None	None	None	None	I
E/V	0.2552	likely_benign	0.2446	benign	-0.061	Destabilizing	0.27	N	0.334	neutral	N	0.503067498	None	None	I
E/W	0.9653	likely_pathogenic	0.9608	pathogenic	0.36	Stabilizing	0.995	D	0.339	neutral	None	None	None	None	I
E/Y	0.783	likely_pathogenic	0.7607	pathogenic	0.309	Stabilizing	0.981	D	0.349	neutral	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.