TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24978	75157;75158;75159	chr2:178571200;178571199;178571198	chr2:179435927;179435926;179435925
N2AB	23337	70234;70235;70236	chr2:178571200;178571199;178571198	chr2:179435927;179435926;179435925
N2A	22410	67453;67454;67455	chr2:178571200;178571199;178571198	chr2:179435927;179435926;179435925
N2B	15913	47962;47963;47964	chr2:178571200;178571199;178571198	chr2:179435927;179435926;179435925
Novex-1	16038	48337;48338;48339	chr2:178571200;178571199;178571198	chr2:179435927;179435926;179435925
Novex-2	16105	48538;48539;48540	chr2:178571200;178571199;178571198	chr2:179435927;179435926;179435925
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: Fn3-69
• Domain position: 71
• Structural Position: 103
• Q(SASA): 0.3385
• 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/Q	rs1708062798	None	0.994	N	0.62	0.277	0.234412748748	gnomAD-4.0.0	1.59182E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85923E-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	0.1539	likely_benign	0.1662	benign	-0.938	Destabilizing	0.919	D	0.528	neutral	N	0.478498809	None	None	N
E/C	0.8477	likely_pathogenic	0.8548	pathogenic	-0.566	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
E/D	0.3773	ambiguous	0.3311	benign	-1.368	Destabilizing	0.958	D	0.41	neutral	N	0.4751939	None	None	N
E/F	0.8384	likely_pathogenic	0.8423	pathogenic	-0.385	Destabilizing	0.995	D	0.804	deleterious	None	None	None	None	N
E/G	0.2671	likely_benign	0.2771	benign	-1.356	Destabilizing	0.988	D	0.709	prob.delet.	N	0.500984384	None	None	N
E/H	0.7797	likely_pathogenic	0.7768	pathogenic	-0.793	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
E/I	0.4545	ambiguous	0.458	ambiguous	0.224	Stabilizing	0.991	D	0.808	deleterious	None	None	None	None	N
E/K	0.4672	ambiguous	0.4946	ambiguous	-0.993	Destabilizing	0.958	D	0.467	neutral	N	0.471697953	None	None	N
E/L	0.5038	ambiguous	0.5188	ambiguous	0.224	Stabilizing	0.982	D	0.733	prob.delet.	None	None	None	None	N
E/M	0.4914	ambiguous	0.5049	ambiguous	0.8	Stabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
E/N	0.5627	ambiguous	0.5413	ambiguous	-1.409	Destabilizing	0.991	D	0.663	neutral	None	None	None	None	N
E/P	0.6437	likely_pathogenic	0.6476	pathogenic	-0.142	Destabilizing	0.995	D	0.803	deleterious	None	None	None	None	N
E/Q	0.2231	likely_benign	0.2386	benign	-1.208	Destabilizing	0.994	D	0.62	neutral	N	0.470078565	None	None	N
E/R	0.5819	likely_pathogenic	0.6097	pathogenic	-0.774	Destabilizing	0.991	D	0.699	prob.neutral	None	None	None	None	N
E/S	0.2824	likely_benign	0.2754	benign	-1.849	Destabilizing	0.938	D	0.471	neutral	None	None	None	None	N
E/T	0.3269	likely_benign	0.3279	benign	-1.495	Destabilizing	0.086	N	0.351	neutral	None	None	None	None	N
E/V	0.2977	likely_benign	0.3065	benign	-0.142	Destabilizing	0.976	D	0.701	prob.neutral	N	0.469473135	None	None	N
E/W	0.9632	likely_pathogenic	0.9647	pathogenic	-0.226	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
E/Y	0.7999	likely_pathogenic	0.7973	pathogenic	-0.156	Destabilizing	0.998	D	0.795	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.