TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18593	56002;56003;56004	chr2:178601127;178601126;178601125	chr2:179465854;179465853;179465852
N2AB	16952	51079;51080;51081	chr2:178601127;178601126;178601125	chr2:179465854;179465853;179465852
N2A	16025	48298;48299;48300	chr2:178601127;178601126;178601125	chr2:179465854;179465853;179465852
N2B	9528	28807;28808;28809	chr2:178601127;178601126;178601125	chr2:179465854;179465853;179465852
Novex-1	9653	29182;29183;29184	chr2:178601127;178601126;178601125	chr2:179465854;179465853;179465852
Novex-2	9720	29383;29384;29385	chr2:178601127;178601126;178601125	chr2:179465854;179465853;179465852
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: Fn3-23
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.343
• 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	None	None	0.999	N	0.599	0.392	0.305086939656	gnomAD-4.0.0	1.71549E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.6422E-05	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	0.5144	ambiguous	0.4923	ambiguous	-0.108	Destabilizing	0.999	D	0.646	neutral	None	None	None	None	N
K/C	0.8474	likely_pathogenic	0.8425	pathogenic	-0.115	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
K/D	0.8128	likely_pathogenic	0.7842	pathogenic	-0.158	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
K/E	0.3307	likely_benign	0.3048	benign	-0.145	Destabilizing	0.999	D	0.599	neutral	N	0.487713178	None	None	N
K/F	0.9728	likely_pathogenic	0.9667	pathogenic	-0.259	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
K/G	0.5116	ambiguous	0.5058	ambiguous	-0.355	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
K/H	0.5864	likely_pathogenic	0.5602	ambiguous	-0.776	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	N
K/I	0.8388	likely_pathogenic	0.8118	pathogenic	0.477	Stabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
K/L	0.7678	likely_pathogenic	0.7406	pathogenic	0.477	Stabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
K/M	0.6145	likely_pathogenic	0.5914	pathogenic	0.509	Stabilizing	1.0	D	0.657	neutral	N	0.502083566	None	None	N
K/N	0.6714	likely_pathogenic	0.6436	pathogenic	0.15	Stabilizing	1.0	D	0.752	deleterious	N	0.505704293	None	None	N
K/P	0.7891	likely_pathogenic	0.7483	pathogenic	0.312	Stabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
K/Q	0.2278	likely_benign	0.2156	benign	-0.111	Destabilizing	1.0	D	0.743	deleterious	N	0.468975701	None	None	N
K/R	0.0813	likely_benign	0.0793	benign	-0.107	Destabilizing	0.999	D	0.541	neutral	N	0.472189152	None	None	N
K/S	0.5827	likely_pathogenic	0.5579	ambiguous	-0.368	Destabilizing	0.999	D	0.68	prob.neutral	None	None	None	None	N
K/T	0.481	ambiguous	0.4602	ambiguous	-0.199	Destabilizing	1.0	D	0.733	prob.delet.	N	0.466947785	None	None	N
K/V	0.7503	likely_pathogenic	0.7221	pathogenic	0.312	Stabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
K/W	0.9395	likely_pathogenic	0.9342	pathogenic	-0.201	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
K/Y	0.9113	likely_pathogenic	0.8999	pathogenic	0.146	Stabilizing	1.0	D	0.724	prob.delet.	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.