TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17665	53218;53219;53220	chr2:178607794;178607793;178607792	chr2:179472521;179472520;179472519
N2AB	16024	48295;48296;48297	chr2:178607794;178607793;178607792	chr2:179472521;179472520;179472519
N2A	15097	45514;45515;45516	chr2:178607794;178607793;178607792	chr2:179472521;179472520;179472519
N2B	8600	26023;26024;26025	chr2:178607794;178607793;178607792	chr2:179472521;179472520;179472519
Novex-1	8725	26398;26399;26400	chr2:178607794;178607793;178607792	chr2:179472521;179472520;179472519
Novex-2	8792	26599;26600;26601	chr2:178607794;178607793;178607792	chr2:179472521;179472520;179472519
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: Fn3-16
• Domain position: 97
• Structural Position: 132
• Q(SASA): 1.3495
• 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/D	rs768659420	-0.203	0.702	N	0.601	0.097	0.316198179892	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
E/D	rs768659420	-0.203	0.702	N	0.601	0.097	0.316198179892	gnomAD-4.0.0	1.59312E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86151E-06	0	0
E/K	None	None	0.919	N	0.677	0.243	0.328752806141	gnomAD-4.0.0	1.59314E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86156E-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
E/A	0.249	likely_benign	0.2651	benign	0.063	Stabilizing	0.958	D	0.693	prob.delet.	N	0.503117852	None	None	N
E/C	0.915	likely_pathogenic	0.9235	pathogenic	-0.103	Destabilizing	0.999	D	0.834	deleterious	None	None	None	None	N
E/D	0.1635	likely_benign	0.1482	benign	-0.336	Destabilizing	0.702	D	0.601	neutral	N	0.424350424	None	None	N
E/F	0.8739	likely_pathogenic	0.8788	pathogenic	-0.03	Destabilizing	0.997	D	0.734	deleterious	None	None	None	None	N
E/G	0.349	ambiguous	0.3625	ambiguous	-0.031	Destabilizing	0.919	D	0.667	prob.neutral	N	0.492908032	None	None	N
E/H	0.7329	likely_pathogenic	0.7595	pathogenic	0.531	Stabilizing	0.991	D	0.561	neutral	None	None	None	None	N
E/I	0.5443	ambiguous	0.5273	ambiguous	0.247	Stabilizing	0.997	D	0.768	deleterious	None	None	None	None	N
E/K	0.3275	likely_benign	0.3418	ambiguous	0.495	Stabilizing	0.919	D	0.677	prob.neutral	N	0.490626626	None	None	N
E/L	0.5409	ambiguous	0.5527	ambiguous	0.247	Stabilizing	0.991	D	0.631	neutral	None	None	None	None	N
E/M	0.6181	likely_pathogenic	0.6306	pathogenic	0.047	Stabilizing	0.999	D	0.725	deleterious	None	None	None	None	N
E/N	0.3693	ambiguous	0.3566	ambiguous	0.277	Stabilizing	0.078	N	0.285	neutral	None	None	None	None	N
E/P	0.5418	ambiguous	0.5693	pathogenic	0.203	Stabilizing	0.997	D	0.645	neutral	None	None	None	None	N
E/Q	0.2655	likely_benign	0.2801	benign	0.281	Stabilizing	0.958	D	0.58	neutral	N	0.48455024	None	None	N
E/R	0.5467	ambiguous	0.5738	pathogenic	0.642	Stabilizing	0.968	D	0.625	neutral	None	None	None	None	N
E/S	0.3334	likely_benign	0.3364	benign	0.159	Stabilizing	0.938	D	0.677	prob.neutral	None	None	None	None	N
E/T	0.4084	ambiguous	0.4006	ambiguous	0.248	Stabilizing	0.938	D	0.714	prob.delet.	None	None	None	None	N
E/V	0.3439	ambiguous	0.339	benign	0.203	Stabilizing	0.996	D	0.598	neutral	N	0.504682411	None	None	N
E/W	0.9653	likely_pathogenic	0.9681	pathogenic	-0.016	Destabilizing	0.999	D	0.852	deleterious	None	None	None	None	N
E/Y	0.8157	likely_pathogenic	0.8263	pathogenic	0.186	Stabilizing	0.997	D	0.741	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.