TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16303	49132;49133;49134	chr2:178614607;178614606;178614605	chr2:179479334;179479333;179479332
N2AB	14662	44209;44210;44211	chr2:178614607;178614606;178614605	chr2:179479334;179479333;179479332
N2A	13735	41428;41429;41430	chr2:178614607;178614606;178614605	chr2:179479334;179479333;179479332
N2B	7238	21937;21938;21939	chr2:178614607;178614606;178614605	chr2:179479334;179479333;179479332
Novex-1	7363	22312;22313;22314	chr2:178614607;178614606;178614605	chr2:179479334;179479333;179479332
Novex-2	7430	22513;22514;22515	chr2:178614607;178614606;178614605	chr2:179479334;179479333;179479332
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-110
• Domain position: 42
• Structural Position: 109
• Q(SASA): 0.9231
• 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	None	None	None	N	0.179	0.1	0.0297737177859	gnomAD-4.0.0	6.84727E-07	None	None	None	None	N	None	2.99419E-05	0	None	0	0	None	0	0	0	0	0
K/R	None	None	0.007	N	0.309	0.118	0.202086224978	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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	0.1528	likely_benign	0.1598	benign	-0.064	Destabilizing	0.004	N	0.294	neutral	None	None	None	None	N
K/C	0.5702	likely_pathogenic	0.5969	pathogenic	-0.547	Destabilizing	0.55	D	0.195	neutral	None	None	None	None	N
K/D	0.149	likely_benign	0.1387	benign	-0.38	Destabilizing	None	N	0.16	neutral	None	None	None	None	N
K/E	0.0831	likely_benign	0.0869	benign	-0.404	Destabilizing	None	N	0.205	neutral	N	0.406047837	None	None	N
K/F	0.718	likely_pathogenic	0.7665	pathogenic	-0.463	Destabilizing	0.245	N	0.257	neutral	None	None	None	None	N
K/G	0.176	likely_benign	0.1966	benign	-0.158	Destabilizing	None	N	0.175	neutral	None	None	None	None	N
K/H	0.2062	likely_benign	0.2207	benign	-0.241	Destabilizing	0.138	N	0.262	neutral	None	None	None	None	N
K/I	0.3522	ambiguous	0.3741	ambiguous	0.1	Stabilizing	0.017	N	0.321	neutral	N	0.453338578	None	None	N
K/L	0.2883	likely_benign	0.327	benign	0.1	Stabilizing	0.009	N	0.245	neutral	None	None	None	None	N
K/M	0.2221	likely_benign	0.2458	benign	-0.201	Destabilizing	0.245	N	0.246	neutral	None	None	None	None	N
K/N	0.1316	likely_benign	0.1253	benign	-0.108	Destabilizing	None	N	0.179	neutral	N	0.433536328	None	None	N
K/P	0.228	likely_benign	0.2408	benign	0.066	Stabilizing	0.085	N	0.381	neutral	None	None	None	None	N
K/Q	0.0919	likely_benign	0.1	benign	-0.245	Destabilizing	None	N	0.269	neutral	N	0.437662062	None	None	N
K/R	0.0939	likely_benign	0.1062	benign	-0.21	Destabilizing	0.007	N	0.309	neutral	N	0.440580202	None	None	N
K/S	0.1322	likely_benign	0.1312	benign	-0.45	Destabilizing	0.004	N	0.196	neutral	None	None	None	None	N
K/T	0.1008	likely_benign	0.1019	benign	-0.371	Destabilizing	None	N	0.197	neutral	N	0.44797481	None	None	N
K/V	0.2846	likely_benign	0.3133	benign	0.066	Stabilizing	0.009	N	0.292	neutral	None	None	None	None	N
K/W	0.7378	likely_pathogenic	0.7952	pathogenic	-0.58	Destabilizing	0.788	D	0.204	neutral	None	None	None	None	N
K/Y	0.5513	ambiguous	0.595	pathogenic	-0.238	Destabilizing	0.245	N	0.293	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.