TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24316	73171;73172;73173	chr2:178573186;178573185;178573184	chr2:179437913;179437912;179437911
N2AB	22675	68248;68249;68250	chr2:178573186;178573185;178573184	chr2:179437913;179437912;179437911
N2A	21748	65467;65468;65469	chr2:178573186;178573185;178573184	chr2:179437913;179437912;179437911
N2B	15251	45976;45977;45978	chr2:178573186;178573185;178573184	chr2:179437913;179437912;179437911
Novex-1	15376	46351;46352;46353	chr2:178573186;178573185;178573184	chr2:179437913;179437912;179437911
Novex-2	15443	46552;46553;46554	chr2:178573186;178573185;178573184	chr2:179437913;179437912;179437911
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-64
• Domain position: 95
• Structural Position: 129
• Q(SASA): 0.2775
• 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/E	rs745520420	0.215	0.997	N	0.815	0.299	0.311691414656	gnomAD-2.1.1	4.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.34E-05	None	0	0	0
K/E	rs745520420	0.215	0.997	N	0.815	0.299	0.311691414656	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.06868E-04	0
K/E	rs745520420	0.215	0.997	N	0.815	0.299	0.311691414656	gnomAD-4.0.0	2.4838E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	3.31236E-05	1.60503E-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
K/A	0.4966	ambiguous	0.4945	ambiguous	-0.194	Destabilizing	0.998	D	0.806	deleterious	None	None	None	None	N
K/C	0.6841	likely_pathogenic	0.7031	pathogenic	-0.314	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
K/D	0.8691	likely_pathogenic	0.8593	pathogenic	0.088	Stabilizing	0.999	D	0.763	deleterious	None	None	None	None	N
K/E	0.3304	likely_benign	0.3143	benign	0.131	Stabilizing	0.997	D	0.815	deleterious	N	0.503738636	None	None	N
K/F	0.7965	likely_pathogenic	0.8028	pathogenic	-0.192	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
K/G	0.7493	likely_pathogenic	0.7376	pathogenic	-0.464	Destabilizing	0.999	D	0.727	deleterious	None	None	None	None	N
K/H	0.3452	ambiguous	0.3619	ambiguous	-0.749	Destabilizing	1.0	D	0.686	prob.delet.	None	None	None	None	N
K/I	0.3474	ambiguous	0.3582	ambiguous	0.459	Stabilizing	0.999	D	0.827	deleterious	None	None	None	None	N
K/L	0.3689	ambiguous	0.3769	ambiguous	0.459	Stabilizing	0.999	D	0.727	deleterious	None	None	None	None	N
K/M	0.2688	likely_benign	0.2671	benign	0.275	Stabilizing	1.0	D	0.679	prob.neutral	N	0.469501771	None	None	N
K/N	0.7004	likely_pathogenic	0.6949	pathogenic	0.014	Stabilizing	0.999	D	0.698	prob.delet.	N	0.517379937	None	None	N
K/P	0.7984	likely_pathogenic	0.8057	pathogenic	0.272	Stabilizing	0.999	D	0.745	deleterious	None	None	None	None	N
K/Q	0.172	likely_benign	0.1697	benign	-0.139	Destabilizing	0.999	D	0.714	prob.delet.	N	0.511550042	None	None	N
K/R	0.0786	likely_benign	0.0754	benign	-0.212	Destabilizing	0.997	D	0.758	deleterious	N	0.450770943	None	None	N
K/S	0.6508	likely_pathogenic	0.6443	pathogenic	-0.563	Destabilizing	0.998	D	0.777	deleterious	None	None	None	None	N
K/T	0.2401	likely_benign	0.2356	benign	-0.345	Destabilizing	0.999	D	0.733	deleterious	N	0.436675777	None	None	N
K/V	0.3128	likely_benign	0.3183	benign	0.272	Stabilizing	0.999	D	0.771	deleterious	None	None	None	None	N
K/W	0.7752	likely_pathogenic	0.7936	pathogenic	-0.129	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
K/Y	0.6778	likely_pathogenic	0.6857	pathogenic	0.191	Stabilizing	1.0	D	0.838	deleterious	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.