TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16945	51058;51059;51060	chr2:178611396;178611395;178611394	chr2:179476123;179476122;179476121
N2AB	15304	46135;46136;46137	chr2:178611396;178611395;178611394	chr2:179476123;179476122;179476121
N2A	14377	43354;43355;43356	chr2:178611396;178611395;178611394	chr2:179476123;179476122;179476121
N2B	7880	23863;23864;23865	chr2:178611396;178611395;178611394	chr2:179476123;179476122;179476121
Novex-1	8005	24238;24239;24240	chr2:178611396;178611395;178611394	chr2:179476123;179476122;179476121
Novex-2	8072	24439;24440;24441	chr2:178611396;178611395;178611394	chr2:179476123;179476122;179476121
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-11
• Domain position: 94
• Structural Position: 126
• Q(SASA): 0.3137
• 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
N/H	None	None	0.998	N	0.713	0.236	0.198526703765	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
N/S	rs1261279387	None	0.952	N	0.467	0.177	0.115124310173	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
N/S	rs1261279387	None	0.952	N	0.467	0.177	0.115124310173	gnomAD-4.0.0	2.56544E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.79175E-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
N/A	0.2356	likely_benign	0.2455	benign	-0.456	Destabilizing	0.963	D	0.659	prob.neutral	None	None	None	None	N
N/C	0.3967	ambiguous	0.4024	ambiguous	0.224	Stabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
N/D	0.1952	likely_benign	0.21	benign	0.048	Stabilizing	0.952	D	0.501	neutral	N	0.471602304	None	None	N
N/E	0.4369	ambiguous	0.4597	ambiguous	0.059	Stabilizing	0.929	D	0.541	neutral	None	None	None	None	N
N/F	0.6485	likely_pathogenic	0.6436	pathogenic	-0.544	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
N/G	0.3469	ambiguous	0.3705	ambiguous	-0.701	Destabilizing	0.963	D	0.472	neutral	None	None	None	None	N
N/H	0.1428	likely_benign	0.1481	benign	-0.594	Destabilizing	0.998	D	0.713	prob.delet.	N	0.469076569	None	None	N
N/I	0.2913	likely_benign	0.2861	benign	0.118	Stabilizing	0.993	D	0.863	deleterious	N	0.450735318	None	None	N
N/K	0.2417	likely_benign	0.2544	benign	-0.062	Destabilizing	0.058	N	0.303	neutral	N	0.41397145	None	None	N
N/L	0.3312	likely_benign	0.3229	benign	0.118	Stabilizing	0.989	D	0.674	prob.neutral	None	None	None	None	N
N/M	0.3771	ambiguous	0.3601	ambiguous	0.381	Stabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
N/P	0.3294	likely_benign	0.3531	ambiguous	-0.044	Destabilizing	0.995	D	0.807	deleterious	None	None	None	None	N
N/Q	0.3669	ambiguous	0.3778	ambiguous	-0.537	Destabilizing	0.989	D	0.722	deleterious	None	None	None	None	N
N/R	0.3309	likely_benign	0.3515	ambiguous	-0.036	Destabilizing	0.979	D	0.66	prob.neutral	None	None	None	None	N
N/S	0.1168	likely_benign	0.121	benign	-0.409	Destabilizing	0.952	D	0.467	neutral	N	0.36906992	None	None	N
N/T	0.1447	likely_benign	0.1464	benign	-0.235	Destabilizing	0.952	D	0.594	neutral	N	0.439617125	None	None	N
N/V	0.2815	likely_benign	0.2768	benign	-0.044	Destabilizing	0.995	D	0.82	deleterious	None	None	None	None	N
N/W	0.8488	likely_pathogenic	0.8488	pathogenic	-0.438	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
N/Y	0.2289	likely_benign	0.229	benign	-0.21	Destabilizing	0.998	D	0.841	deleterious	N	0.460586052	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.