TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24969	75130;75131;75132	chr2:178571227;178571226;178571225	chr2:179435954;179435953;179435952
N2AB	23328	70207;70208;70209	chr2:178571227;178571226;178571225	chr2:179435954;179435953;179435952
N2A	22401	67426;67427;67428	chr2:178571227;178571226;178571225	chr2:179435954;179435953;179435952
N2B	15904	47935;47936;47937	chr2:178571227;178571226;178571225	chr2:179435954;179435953;179435952
Novex-1	16029	48310;48311;48312	chr2:178571227;178571226;178571225	chr2:179435954;179435953;179435952
Novex-2	16096	48511;48512;48513	chr2:178571227;178571226;178571225	chr2:179435954;179435953;179435952
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-69
• Domain position: 62
• Structural Position: 92
• Q(SASA): 0.4345
• 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/N	rs1708070929	None	0.988	N	0.675	0.254	0.158396225186	gnomAD-4.0.0	3.18353E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88267E-05	0	0	0	3.02517E-05

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	0.5823	likely_pathogenic	0.6117	pathogenic	-0.389	Destabilizing	0.968	D	0.616	neutral	None	None	None	None	N
K/C	0.7011	likely_pathogenic	0.7138	pathogenic	-0.479	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
K/D	0.8992	likely_pathogenic	0.9095	pathogenic	0.269	Stabilizing	0.995	D	0.764	deleterious	None	None	None	None	N
K/E	0.4297	ambiguous	0.4697	ambiguous	0.318	Stabilizing	0.958	D	0.528	neutral	N	0.51567057	None	None	N
K/F	0.8436	likely_pathogenic	0.8629	pathogenic	-0.425	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
K/G	0.7657	likely_pathogenic	0.7897	pathogenic	-0.654	Destabilizing	0.991	D	0.701	prob.neutral	None	None	None	None	N
K/H	0.3583	ambiguous	0.3642	ambiguous	-0.951	Destabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	N
K/I	0.412	ambiguous	0.4315	ambiguous	0.252	Stabilizing	0.995	D	0.752	deleterious	None	None	None	None	N
K/L	0.4605	ambiguous	0.4757	ambiguous	0.252	Stabilizing	0.991	D	0.701	prob.neutral	None	None	None	None	N
K/M	0.3439	ambiguous	0.3568	ambiguous	0.131	Stabilizing	0.999	D	0.739	prob.delet.	N	0.478370224	None	None	N
K/N	0.7412	likely_pathogenic	0.768	pathogenic	-0.052	Destabilizing	0.988	D	0.675	neutral	N	0.46625345	None	None	N
K/P	0.8414	likely_pathogenic	0.8605	pathogenic	0.068	Stabilizing	0.998	D	0.767	deleterious	None	None	None	None	N
K/Q	0.181	likely_benign	0.1884	benign	-0.207	Destabilizing	0.988	D	0.649	neutral	N	0.468886796	None	None	N
K/R	0.0745	likely_benign	0.0745	benign	-0.23	Destabilizing	0.142	N	0.343	neutral	N	0.463743027	None	None	N
K/S	0.6725	likely_pathogenic	0.6952	pathogenic	-0.717	Destabilizing	0.968	D	0.599	neutral	None	None	None	None	N
K/T	0.2965	likely_benign	0.2959	benign	-0.485	Destabilizing	0.988	D	0.753	deleterious	N	0.423352268	None	None	N
K/V	0.4039	ambiguous	0.4246	ambiguous	0.068	Stabilizing	0.995	D	0.756	deleterious	None	None	None	None	N
K/W	0.8099	likely_pathogenic	0.824	pathogenic	-0.314	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
K/Y	0.7531	likely_pathogenic	0.7693	pathogenic	0.004	Stabilizing	0.998	D	0.764	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.