TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25680	77263;77264;77265	chr2:178569094;178569093;178569092	chr2:179433821;179433820;179433819
N2AB	24039	72340;72341;72342	chr2:178569094;178569093;178569092	chr2:179433821;179433820;179433819
N2A	23112	69559;69560;69561	chr2:178569094;178569093;178569092	chr2:179433821;179433820;179433819
N2B	16615	50068;50069;50070	chr2:178569094;178569093;178569092	chr2:179433821;179433820;179433819
Novex-1	16740	50443;50444;50445	chr2:178569094;178569093;178569092	chr2:179433821;179433820;179433819
Novex-2	16807	50644;50645;50646	chr2:178569094;178569093;178569092	chr2:179433821;179433820;179433819
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-74
• Domain position: 80
• Structural Position: 113
• Q(SASA): 0.5018
• 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
E/D	None	None	0.941	N	0.375	0.22	0.336400405673	gnomAD-4.0.0	6.84361E-07	None	None	None	None	I	None	2.99007E-05	0	None	0	0	None	0	0	0	0	0
E/K	rs1385780245	0.548	0.996	N	0.572	0.415	0.307966526162	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
E/K	rs1385780245	0.548	0.996	N	0.572	0.415	0.307966526162	gnomAD-4.0.0	3.1841E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.71961E-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
E/A	0.3375	likely_benign	0.3564	ambiguous	-0.753	Destabilizing	0.992	D	0.59	neutral	N	0.514785136	None	None	I
E/C	0.9565	likely_pathogenic	0.9551	pathogenic	-0.318	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	I
E/D	0.2126	likely_benign	0.2255	benign	-0.497	Destabilizing	0.941	D	0.375	neutral	N	0.520057669	None	None	I
E/F	0.9518	likely_pathogenic	0.9579	pathogenic	-0.388	Destabilizing	1.0	D	0.614	neutral	None	None	None	None	I
E/G	0.5614	ambiguous	0.5845	pathogenic	-0.974	Destabilizing	0.999	D	0.581	neutral	N	0.476450304	None	None	I
E/H	0.8467	likely_pathogenic	0.8593	pathogenic	-0.073	Destabilizing	1.0	D	0.626	neutral	None	None	None	None	I
E/I	0.5222	ambiguous	0.5396	ambiguous	-0.185	Destabilizing	0.998	D	0.636	neutral	None	None	None	None	I
E/K	0.4369	ambiguous	0.4639	ambiguous	0.134	Stabilizing	0.996	D	0.572	neutral	N	0.461972158	None	None	I
E/L	0.7391	likely_pathogenic	0.7586	pathogenic	-0.185	Destabilizing	0.998	D	0.621	neutral	None	None	None	None	I
E/M	0.7266	likely_pathogenic	0.7452	pathogenic	-0.026	Destabilizing	0.997	D	0.613	neutral	None	None	None	None	I
E/N	0.5448	ambiguous	0.5746	pathogenic	-0.411	Destabilizing	0.996	D	0.676	prob.neutral	None	None	None	None	I
E/P	0.8715	likely_pathogenic	0.8792	pathogenic	-0.356	Destabilizing	0.987	D	0.615	neutral	None	None	None	None	I
E/Q	0.3418	ambiguous	0.3648	ambiguous	-0.347	Destabilizing	0.998	D	0.563	neutral	N	0.473988904	None	None	I
E/R	0.6502	likely_pathogenic	0.6738	pathogenic	0.453	Stabilizing	0.999	D	0.673	neutral	None	None	None	None	I
E/S	0.4769	ambiguous	0.5108	ambiguous	-0.554	Destabilizing	0.994	D	0.619	neutral	None	None	None	None	I
E/T	0.459	ambiguous	0.483	ambiguous	-0.357	Destabilizing	0.999	D	0.631	neutral	None	None	None	None	I
E/V	0.4074	ambiguous	0.4228	ambiguous	-0.356	Destabilizing	0.996	D	0.624	neutral	N	0.47795215	None	None	I
E/W	0.9899	likely_pathogenic	0.9912	pathogenic	-0.102	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	I
E/Y	0.9016	likely_pathogenic	0.9163	pathogenic	-0.118	Destabilizing	1.0	D	0.619	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.