TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17008	51247;51248;51249	chr2:178611107;178611106;178611105	chr2:179475834;179475833;179475832
N2AB	15367	46324;46325;46326	chr2:178611107;178611106;178611105	chr2:179475834;179475833;179475832
N2A	14440	43543;43544;43545	chr2:178611107;178611106;178611105	chr2:179475834;179475833;179475832
N2B	7943	24052;24053;24054	chr2:178611107;178611106;178611105	chr2:179475834;179475833;179475832
Novex-1	8068	24427;24428;24429	chr2:178611107;178611106;178611105	chr2:179475834;179475833;179475832
Novex-2	8135	24628;24629;24630	chr2:178611107;178611106;178611105	chr2:179475834;179475833;179475832
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-111
• Domain position: 54
• Structural Position: 134
• Q(SASA): 0.5235
• 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
I/V	None	None	None	N	0.128	0.046	0.344945010812	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

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
I/A	0.1958	likely_benign	0.1985	benign	-1.212	Destabilizing	None	N	0.199	neutral	None	None	None	None	N
I/C	0.4677	ambiguous	0.4652	ambiguous	-0.477	Destabilizing	0.667	D	0.429	neutral	None	None	None	None	N
I/D	0.4356	ambiguous	0.4248	ambiguous	-0.541	Destabilizing	0.22	N	0.486	neutral	None	None	None	None	N
I/E	0.4001	ambiguous	0.4032	ambiguous	-0.581	Destabilizing	0.22	N	0.509	neutral	None	None	None	None	N
I/F	0.1153	likely_benign	0.1199	benign	-0.927	Destabilizing	0.001	N	0.203	neutral	N	0.465506486	None	None	N
I/G	0.4026	ambiguous	0.3912	ambiguous	-1.474	Destabilizing	0.124	N	0.459	neutral	None	None	None	None	N
I/H	0.3062	likely_benign	0.3053	benign	-0.696	Destabilizing	0.958	D	0.463	neutral	None	None	None	None	N
I/K	0.2627	likely_benign	0.2675	benign	-0.673	Destabilizing	0.22	N	0.506	neutral	None	None	None	None	N
I/L	0.0962	likely_benign	0.0949	benign	-0.597	Destabilizing	0.019	N	0.193	neutral	N	0.472427052	None	None	N
I/M	0.0988	likely_benign	0.1035	benign	-0.368	Destabilizing	0.427	N	0.405	neutral	N	0.509217456	None	None	N
I/N	0.1432	likely_benign	0.1386	benign	-0.387	Destabilizing	0.427	N	0.488	neutral	N	0.377726886	None	None	N
I/P	0.6072	likely_pathogenic	0.5601	ambiguous	-0.769	Destabilizing	0.667	D	0.493	neutral	None	None	None	None	N
I/Q	0.2935	likely_benign	0.2973	benign	-0.593	Destabilizing	0.667	D	0.484	neutral	None	None	None	None	N
I/R	0.2096	likely_benign	0.2026	benign	-0.075	Destabilizing	0.497	N	0.49	neutral	None	None	None	None	N
I/S	0.1561	likely_benign	0.1486	benign	-0.929	Destabilizing	0.042	N	0.445	neutral	N	0.436892007	None	None	N
I/T	0.1318	likely_benign	0.1364	benign	-0.86	Destabilizing	None	N	0.196	neutral	N	0.365964753	None	None	N
I/V	0.0712	likely_benign	0.073	benign	-0.769	Destabilizing	None	N	0.128	neutral	N	0.459876114	None	None	N
I/W	0.5966	likely_pathogenic	0.6005	pathogenic	-0.981	Destabilizing	0.958	D	0.468	neutral	None	None	None	None	N
I/Y	0.3111	likely_benign	0.3118	benign	-0.756	Destabilizing	0.331	N	0.442	neutral	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.