TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7000	21223;21224;21225	chr2:178724377;178724376;178724375	chr2:179589104;179589103;179589102
N2AB	6683	20272;20273;20274	chr2:178724377;178724376;178724375	chr2:179589104;179589103;179589102
N2A	5756	17491;17492;17493	chr2:178724377;178724376;178724375	chr2:179589104;179589103;179589102
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-54
• Domain position: 53
• Structural Position: 131
• Q(SASA): 0.5189
• 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/D	rs1173819966	None	0.015	N	0.098	0.104	0.0716867268079	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
N/D	rs1173819966	None	0.015	N	0.098	0.104	0.0716867268079	gnomAD-4.0.0	2.56303E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.78801E-06	0	0
N/I	rs764035021	0.299	0.996	N	0.45	0.421	0.463243292966	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
N/I	rs764035021	0.299	0.996	N	0.45	0.421	0.463243292966	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
N/I	rs764035021	0.299	0.996	N	0.45	0.421	0.463243292966	gnomAD-4.0.0	1.85939E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.54322E-06	0	0
N/S	rs764035021	-0.305	0.826	N	0.355	0.209	0.0806252709748	gnomAD-2.1.1	9.25E-05	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	7.19095E-04	None	0	0	0
N/S	rs764035021	-0.305	0.826	N	0.355	0.209	0.0806252709748	gnomAD-3.1.2	6.57E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07125E-03	0
N/S	rs764035021	-0.305	0.826	N	0.355	0.209	0.0806252709748	gnomAD-4.0.0	6.136E-05	None	None	None	None	N	None	0	1.66783E-05	None	0	0	None	0	0	4.2387E-06	9.55267E-04	9.61015E-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
N/A	0.4651	ambiguous	0.474	ambiguous	-0.118	Destabilizing	0.939	D	0.377	neutral	None	None	None	None	N
N/C	0.5569	ambiguous	0.5679	pathogenic	-0.01	Destabilizing	0.999	D	0.472	neutral	None	None	None	None	N
N/D	0.1327	likely_benign	0.1501	benign	0.27	Stabilizing	0.015	N	0.098	neutral	N	0.429520518	None	None	N
N/E	0.4243	ambiguous	0.454	ambiguous	0.239	Stabilizing	0.759	D	0.321	neutral	None	None	None	None	N
N/F	0.8595	likely_pathogenic	0.8694	pathogenic	-0.713	Destabilizing	0.997	D	0.443	neutral	None	None	None	None	N
N/G	0.2727	likely_benign	0.2835	benign	-0.232	Destabilizing	0.927	D	0.325	neutral	None	None	None	None	N
N/H	0.1073	likely_benign	0.1132	benign	-0.134	Destabilizing	0.996	D	0.427	neutral	N	0.470639209	None	None	N
N/I	0.782	likely_pathogenic	0.7765	pathogenic	0.085	Stabilizing	0.996	D	0.45	neutral	N	0.494689504	None	None	N
N/K	0.3187	likely_benign	0.3203	benign	0.154	Stabilizing	0.134	N	0.125	neutral	N	0.448858427	None	None	N
N/L	0.5518	ambiguous	0.5518	ambiguous	0.085	Stabilizing	0.991	D	0.413	neutral	None	None	None	None	N
N/M	0.6969	likely_pathogenic	0.6962	pathogenic	-0.101	Destabilizing	0.999	D	0.435	neutral	None	None	None	None	N
N/P	0.8635	likely_pathogenic	0.8261	pathogenic	0.041	Stabilizing	0.997	D	0.431	neutral	None	None	None	None	N
N/Q	0.2986	likely_benign	0.3067	benign	-0.254	Destabilizing	0.982	D	0.361	neutral	None	None	None	None	N
N/R	0.3127	likely_benign	0.3129	benign	0.245	Stabilizing	0.884	D	0.352	neutral	None	None	None	None	N
N/S	0.1154	likely_benign	0.1087	benign	-0.129	Destabilizing	0.826	D	0.355	neutral	N	0.419978315	None	None	N
N/T	0.4137	ambiguous	0.417	ambiguous	-0.033	Destabilizing	0.959	D	0.287	neutral	N	0.459518138	None	None	N
N/V	0.7499	likely_pathogenic	0.7418	pathogenic	0.041	Stabilizing	0.991	D	0.422	neutral	None	None	None	None	N
N/W	0.8636	likely_pathogenic	0.8756	pathogenic	-0.858	Destabilizing	0.999	D	0.58	neutral	None	None	None	None	N
N/Y	0.3185	likely_benign	0.3364	benign	-0.506	Destabilizing	0.996	D	0.429	neutral	N	0.500615399	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.