TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4773	14542;14543;14544	chr2:178738136;178738135;178738134	chr2:179602863;179602862;179602861
N2AB	4456	13591;13592;13593	chr2:178738136;178738135;178738134	chr2:179602863;179602862;179602861
N2A	3529	10810;10811;10812	chr2:178738136;178738135;178738134	chr2:179602863;179602862;179602861
N2B	4410	13453;13454;13455	chr2:178738136;178738135;178738134	chr2:179602863;179602862;179602861
Novex-1	4535	13828;13829;13830	chr2:178738136;178738135;178738134	chr2:179602863;179602862;179602861
Novex-2	4602	14029;14030;14031	chr2:178738136;178738135;178738134	chr2:179602863;179602862;179602861
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-30
• Domain position: 74
• Structural Position: 157
• Q(SASA): 0.4855
• 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
K/E	None	None	0.698	N	0.588	0.352	0.281780670237	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
K/R	None	None	0.014	N	0.379	0.2	0.349647731962	gnomAD-4.0.0	1.59133E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85838E-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
K/A	0.6246	likely_pathogenic	0.8119	pathogenic	-0.982	Destabilizing	0.754	D	0.652	neutral	None	None	None	None	N
K/C	0.8306	likely_pathogenic	0.9077	pathogenic	-1.151	Destabilizing	0.998	D	0.72	prob.delet.	None	None	None	None	N
K/D	0.9184	likely_pathogenic	0.9714	pathogenic	-0.406	Destabilizing	0.956	D	0.72	prob.delet.	None	None	None	None	N
K/E	0.2774	likely_benign	0.5169	ambiguous	-0.288	Destabilizing	0.698	D	0.588	neutral	N	0.467255555	None	None	N
K/F	0.8717	likely_pathogenic	0.9449	pathogenic	-0.9	Destabilizing	0.998	D	0.763	deleterious	None	None	None	None	N
K/G	0.8661	likely_pathogenic	0.947	pathogenic	-1.324	Destabilizing	0.86	D	0.71	prob.delet.	None	None	None	None	N
K/H	0.4623	ambiguous	0.6197	pathogenic	-1.68	Destabilizing	0.994	D	0.723	prob.delet.	None	None	None	None	N
K/I	0.308	likely_benign	0.4715	ambiguous	-0.093	Destabilizing	0.971	D	0.769	deleterious	N	0.468522568	None	None	N
K/L	0.4238	ambiguous	0.6263	pathogenic	-0.093	Destabilizing	0.86	D	0.71	prob.delet.	None	None	None	None	N
K/M	0.2566	likely_benign	0.3996	ambiguous	-0.088	Destabilizing	0.994	D	0.721	prob.delet.	None	None	None	None	N
K/N	0.7523	likely_pathogenic	0.8998	pathogenic	-0.701	Destabilizing	0.942	D	0.661	neutral	N	0.468322411	None	None	N
K/P	0.9917	likely_pathogenic	0.9967	pathogenic	-0.362	Destabilizing	0.978	D	0.757	deleterious	None	None	None	None	N
K/Q	0.173	likely_benign	0.2725	benign	-0.859	Destabilizing	0.126	N	0.332	neutral	N	0.428987201	None	None	N
K/R	0.1002	likely_benign	0.1163	benign	-0.619	Destabilizing	0.014	N	0.379	neutral	N	0.467255555	None	None	N
K/S	0.7116	likely_pathogenic	0.8709	pathogenic	-1.472	Destabilizing	0.754	D	0.613	neutral	None	None	None	None	N
K/T	0.2657	likely_benign	0.4313	ambiguous	-1.141	Destabilizing	0.942	D	0.715	prob.delet.	N	0.443383317	None	None	N
K/V	0.2947	likely_benign	0.4442	ambiguous	-0.362	Destabilizing	0.956	D	0.744	deleterious	None	None	None	None	N
K/W	0.8854	likely_pathogenic	0.945	pathogenic	-0.705	Destabilizing	0.998	D	0.683	prob.neutral	None	None	None	None	N
K/Y	0.7812	likely_pathogenic	0.8934	pathogenic	-0.365	Destabilizing	0.978	D	0.771	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.