TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26826	80701;80702;80703	chr2:178565656;178565655;178565654	chr2:179430383;179430382;179430381
N2AB	25185	75778;75779;75780	chr2:178565656;178565655;178565654	chr2:179430383;179430382;179430381
N2A	24258	72997;72998;72999	chr2:178565656;178565655;178565654	chr2:179430383;179430382;179430381
N2B	17761	53506;53507;53508	chr2:178565656;178565655;178565654	chr2:179430383;179430382;179430381
Novex-1	17886	53881;53882;53883	chr2:178565656;178565655;178565654	chr2:179430383;179430382;179430381
Novex-2	17953	54082;54083;54084	chr2:178565656;178565655;178565654	chr2:179430383;179430382;179430381
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: Fn3-83
• Domain position: 47
• Structural Position: 64
• Q(SASA): 0.7602
• Predicted PPI site: I

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	rs1318267898	0.426	0.006	N	0.207	0.072	0.110078149338	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
K/N	rs1318267898	0.426	0.006	N	0.207	0.072	0.110078149338	gnomAD-4.0.0	5.47424E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	7.19656E-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
K/A	0.2647	likely_benign	0.2153	benign	0.08	Stabilizing	0.339	N	0.369	neutral	None	None	None	None	I
K/C	0.5796	likely_pathogenic	0.5609	ambiguous	-0.245	Destabilizing	0.995	D	0.298	neutral	None	None	None	None	I
K/D	0.3726	ambiguous	0.2996	benign	-0.005	Destabilizing	0.008	N	0.237	neutral	None	None	None	None	I
K/E	0.163	likely_benign	0.1288	benign	-0.002	Destabilizing	0.003	N	0.11	neutral	N	0.344856986	None	None	I
K/F	0.6494	likely_pathogenic	0.5815	pathogenic	-0.17	Destabilizing	0.955	D	0.303	neutral	None	None	None	None	I
K/G	0.3467	ambiguous	0.3042	benign	-0.092	Destabilizing	0.339	N	0.3	neutral	None	None	None	None	I
K/H	0.2252	likely_benign	0.2093	benign	-0.25	Destabilizing	0.783	D	0.294	neutral	None	None	None	None	I
K/I	0.2573	likely_benign	0.213	benign	0.452	Stabilizing	0.282	N	0.324	neutral	N	0.471074431	None	None	I
K/L	0.2978	likely_benign	0.251	benign	0.452	Stabilizing	0.068	N	0.353	neutral	None	None	None	None	I
K/M	0.1779	likely_benign	0.1454	benign	0.109	Stabilizing	0.96	D	0.303	neutral	None	None	None	None	I
K/N	0.2418	likely_benign	0.1857	benign	0.217	Stabilizing	0.006	N	0.207	neutral	N	0.441482243	None	None	I
K/P	0.7131	likely_pathogenic	0.6754	pathogenic	0.354	Stabilizing	0.834	D	0.344	neutral	None	None	None	None	I
K/Q	0.114	likely_benign	0.1016	benign	0.077	Stabilizing	0.185	N	0.293	neutral	N	0.407735028	None	None	I
K/R	0.0867	likely_benign	0.085	benign	0.023	Stabilizing	0.258	N	0.293	neutral	N	0.400635698	None	None	I
K/S	0.2938	likely_benign	0.2358	benign	-0.212	Destabilizing	0.088	N	0.194	neutral	None	None	None	None	I
K/T	0.126	likely_benign	0.1031	benign	-0.072	Destabilizing	0.22	N	0.343	neutral	N	0.423973917	None	None	I
K/V	0.2431	likely_benign	0.207	benign	0.354	Stabilizing	0.163	N	0.337	neutral	None	None	None	None	I
K/W	0.6723	likely_pathogenic	0.6521	pathogenic	-0.242	Destabilizing	0.997	D	0.375	neutral	None	None	None	None	I
K/Y	0.4688	ambiguous	0.4247	ambiguous	0.119	Stabilizing	0.715	D	0.303	neutral	None	None	None	None	I

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.