TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21817	65674;65675;65676	chr2:178583733;178583732;178583731	chr2:179448460;179448459;179448458
N2AB	20176	60751;60752;60753	chr2:178583733;178583732;178583731	chr2:179448460;179448459;179448458
N2A	19249	57970;57971;57972	chr2:178583733;178583732;178583731	chr2:179448460;179448459;179448458
N2B	12752	38479;38480;38481	chr2:178583733;178583732;178583731	chr2:179448460;179448459;179448458
Novex-1	12877	38854;38855;38856	chr2:178583733;178583732;178583731	chr2:179448460;179448459;179448458
Novex-2	12944	39055;39056;39057	chr2:178583733;178583732;178583731	chr2:179448460;179448459;179448458
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: Fn3-46
• Domain position: 61
• Structural Position: 89
• Q(SASA): 0.2565
• 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/K	rs751947173	-0.091	0.999	N	0.617	0.438	0.32714864917	gnomAD-2.1.1	1.08E-05	None	None	None	None	N	None	0	8.54E-05	None	0	0	None	0	None	0	0	0
E/K	rs751947173	-0.091	0.999	N	0.617	0.438	0.32714864917	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/K	rs751947173	-0.091	0.999	N	0.617	0.438	0.32714864917	gnomAD-4.0.0	2.48111E-06	None	None	None	None	N	None	0	3.34046E-05	None	0	0	None	0	0	1.69612E-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	0.2533	likely_benign	0.2246	benign	0.21	Stabilizing	0.999	D	0.685	prob.neutral	N	0.495484512	None	None	N
E/C	0.8413	likely_pathogenic	0.8087	pathogenic	0.122	Stabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
E/D	0.578	likely_pathogenic	0.5327	ambiguous	-1.272	Destabilizing	0.999	D	0.565	neutral	N	0.490078692	None	None	N
E/F	0.9497	likely_pathogenic	0.936	pathogenic	0.958	Stabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
E/G	0.2978	likely_benign	0.2832	benign	-0.262	Destabilizing	1.0	D	0.725	prob.delet.	N	0.467944836	None	None	N
E/H	0.8697	likely_pathogenic	0.8363	pathogenic	0.581	Stabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
E/I	0.7422	likely_pathogenic	0.6782	pathogenic	1.519	Stabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
E/K	0.4774	ambiguous	0.425	ambiguous	-0.275	Destabilizing	0.999	D	0.617	neutral	N	0.466124397	None	None	N
E/L	0.5917	likely_pathogenic	0.5275	ambiguous	1.519	Stabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
E/M	0.6004	likely_pathogenic	0.5575	ambiguous	1.863	Stabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
E/N	0.5813	likely_pathogenic	0.5345	ambiguous	-0.92	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
E/P	0.686	likely_pathogenic	0.6535	pathogenic	1.107	Stabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
E/Q	0.2821	likely_benign	0.2385	benign	-0.589	Destabilizing	1.0	D	0.649	neutral	N	0.499255536	None	None	N
E/R	0.6004	likely_pathogenic	0.5566	ambiguous	-0.185	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	N
E/S	0.535	ambiguous	0.4863	ambiguous	-1.305	Destabilizing	0.999	D	0.639	neutral	None	None	None	None	N
E/T	0.3474	ambiguous	0.3082	benign	-0.885	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
E/V	0.4445	ambiguous	0.3958	ambiguous	1.107	Stabilizing	1.0	D	0.735	prob.delet.	N	0.507797661	None	None	N
E/W	0.9806	likely_pathogenic	0.9786	pathogenic	0.926	Stabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
E/Y	0.9017	likely_pathogenic	0.8828	pathogenic	1.19	Stabilizing	1.0	D	0.767	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.