TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16565	49918;49919;49920	chr2:178613028;178613027;178613026	chr2:179477755;179477754;179477753
N2AB	14924	44995;44996;44997	chr2:178613028;178613027;178613026	chr2:179477755;179477754;179477753
N2A	13997	42214;42215;42216	chr2:178613028;178613027;178613026	chr2:179477755;179477754;179477753
N2B	7500	22723;22724;22725	chr2:178613028;178613027;178613026	chr2:179477755;179477754;179477753
Novex-1	7625	23098;23099;23100	chr2:178613028;178613027;178613026	chr2:179477755;179477754;179477753
Novex-2	7692	23299;23300;23301	chr2:178613028;178613027;178613026	chr2:179477755;179477754;179477753
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: Fn3-8
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.3509
• 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	rs774229828	-0.049	0.41	N	0.472	0.256	0.225215365344	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
K/E	rs774229828	-0.049	0.41	N	0.472	0.256	0.225215365344	gnomAD-4.0.0	6.846E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99826E-07	0	0
K/Q	None	None	0.83	N	0.7	0.29	0.247322355667	gnomAD-4.0.0	6.846E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15977E-05	0
K/R	rs770853524	0.054	0.01	N	0.304	0.097	0.197625483188	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
K/R	rs770853524	0.054	0.01	N	0.304	0.097	0.197625483188	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/R	rs770853524	0.054	0.01	N	0.304	0.097	0.197625483188	gnomAD-4.0.0	4.34016E-06	None	None	None	None	N	None	8.00299E-05	0	None	0	0	None	0	0	8.47994E-07	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	0.5868	likely_pathogenic	0.555	ambiguous	-0.132	Destabilizing	0.648	D	0.535	neutral	None	None	None	None	N
K/C	0.8242	likely_pathogenic	0.7528	pathogenic	-0.238	Destabilizing	0.993	D	0.796	deleterious	None	None	None	None	N
K/D	0.8163	likely_pathogenic	0.7763	pathogenic	0.057	Stabilizing	0.866	D	0.727	prob.delet.	None	None	None	None	N
K/E	0.4107	ambiguous	0.3998	ambiguous	0.065	Stabilizing	0.41	N	0.472	neutral	N	0.475857072	None	None	N
K/F	0.9196	likely_pathogenic	0.8838	pathogenic	-0.348	Destabilizing	0.98	D	0.791	deleterious	None	None	None	None	N
K/G	0.6239	likely_pathogenic	0.5526	ambiguous	-0.354	Destabilizing	0.866	D	0.679	prob.neutral	None	None	None	None	N
K/H	0.5467	ambiguous	0.4379	ambiguous	-0.747	Destabilizing	0.98	D	0.711	prob.delet.	None	None	None	None	N
K/I	0.6496	likely_pathogenic	0.587	pathogenic	0.376	Stabilizing	0.908	D	0.805	deleterious	D	0.620498007	None	None	N
K/L	0.6037	likely_pathogenic	0.5251	ambiguous	0.376	Stabilizing	0.866	D	0.679	prob.neutral	None	None	None	None	N
K/M	0.4525	ambiguous	0.4289	ambiguous	0.36	Stabilizing	0.993	D	0.713	prob.delet.	None	None	None	None	N
K/N	0.6535	likely_pathogenic	0.6021	pathogenic	0.19	Stabilizing	0.83	D	0.705	prob.neutral	N	0.473466138	None	None	N
K/P	0.7212	likely_pathogenic	0.6796	pathogenic	0.236	Stabilizing	0.929	D	0.715	prob.delet.	None	None	None	None	N
K/Q	0.2426	likely_benign	0.2104	benign	-0.062	Destabilizing	0.83	D	0.7	prob.neutral	N	0.503389047	None	None	N
K/R	0.0869	likely_benign	0.0725	benign	-0.064	Destabilizing	0.01	N	0.304	neutral	N	0.480996959	None	None	N
K/S	0.6491	likely_pathogenic	0.6035	pathogenic	-0.375	Destabilizing	0.648	D	0.595	neutral	None	None	None	None	N
K/T	0.4354	ambiguous	0.427	ambiguous	-0.211	Destabilizing	0.83	D	0.68	prob.neutral	N	0.508833859	None	None	N
K/V	0.6137	likely_pathogenic	0.5606	ambiguous	0.236	Stabilizing	0.866	D	0.737	prob.delet.	None	None	None	None	N
K/W	0.8888	likely_pathogenic	0.8238	pathogenic	-0.283	Destabilizing	0.993	D	0.801	deleterious	None	None	None	None	N
K/Y	0.84	likely_pathogenic	0.772	pathogenic	0.074	Stabilizing	0.929	D	0.79	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.