TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19528	58807;58808;58809	chr2:178593718;178593717;178593716	chr2:179458445;179458444;179458443
N2AB	17887	53884;53885;53886	chr2:178593718;178593717;178593716	chr2:179458445;179458444;179458443
N2A	16960	51103;51104;51105	chr2:178593718;178593717;178593716	chr2:179458445;179458444;179458443
N2B	10463	31612;31613;31614	chr2:178593718;178593717;178593716	chr2:179458445;179458444;179458443
Novex-1	10588	31987;31988;31989	chr2:178593718;178593717;178593716	chr2:179458445;179458444;179458443
Novex-2	10655	32188;32189;32190	chr2:178593718;178593717;178593716	chr2:179458445;179458444;179458443
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Fn3-29
• Domain position: 50
• Structural Position: 66
• Q(SASA): 0.6176
• 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
M/T	None	None	0.324	N	0.352	0.265	0.710242159801	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	2.625E-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
M/A	0.5046	ambiguous	0.4561	ambiguous	-1.714	Destabilizing	0.207	N	0.377	neutral	None	None	None	None	N
M/C	0.7816	likely_pathogenic	0.6999	pathogenic	-1.223	Destabilizing	0.981	D	0.355	neutral	None	None	None	None	N
M/D	0.8593	likely_pathogenic	0.8303	pathogenic	-0.641	Destabilizing	0.818	D	0.376	neutral	None	None	None	None	N
M/E	0.5573	ambiguous	0.5081	ambiguous	-0.6	Destabilizing	0.818	D	0.361	neutral	None	None	None	None	N
M/F	0.35	ambiguous	0.3105	benign	-0.667	Destabilizing	0.241	N	0.341	neutral	None	None	None	None	N
M/G	0.712	likely_pathogenic	0.7035	pathogenic	-2.015	Highly Destabilizing	0.563	D	0.366	neutral	None	None	None	None	N
M/H	0.5476	ambiguous	0.4735	ambiguous	-0.94	Destabilizing	0.981	D	0.34	neutral	None	None	None	None	N
M/I	0.2698	likely_benign	0.2391	benign	-0.932	Destabilizing	0.001	N	0.111	neutral	N	0.41352485	None	None	N
M/K	0.3261	likely_benign	0.2771	benign	-0.725	Destabilizing	0.492	N	0.369	neutral	N	0.400112836	None	None	N
M/L	0.1312	likely_benign	0.1087	benign	-0.932	Destabilizing	0.001	N	0.095	neutral	N	0.415333004	None	None	N
M/N	0.4596	ambiguous	0.4451	ambiguous	-0.644	Destabilizing	0.932	D	0.371	neutral	None	None	None	None	N
M/P	0.9711	likely_pathogenic	0.9661	pathogenic	-1.168	Destabilizing	0.932	D	0.371	neutral	None	None	None	None	N
M/Q	0.2984	likely_benign	0.2568	benign	-0.711	Destabilizing	0.932	D	0.377	neutral	None	None	None	None	N
M/R	0.3984	ambiguous	0.3267	benign	-0.156	Destabilizing	0.773	D	0.385	neutral	N	0.430686459	None	None	N
M/S	0.4397	ambiguous	0.4098	ambiguous	-1.218	Destabilizing	0.563	D	0.341	neutral	None	None	None	None	N
M/T	0.2961	likely_benign	0.2599	benign	-1.072	Destabilizing	0.324	N	0.352	neutral	N	0.38148979	None	None	N
M/V	0.1256	likely_benign	0.1144	benign	-1.168	Destabilizing	0.015	N	0.175	neutral	N	0.410772547	None	None	N
M/W	0.7208	likely_pathogenic	0.6308	pathogenic	-0.607	Destabilizing	0.981	D	0.369	neutral	None	None	None	None	N
M/Y	0.5607	ambiguous	0.5076	ambiguous	-0.654	Destabilizing	0.818	D	0.382	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.