TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28446	85561;85562;85563	chr2:178560796;178560795;178560794	chr2:179425523;179425522;179425521
N2AB	26805	80638;80639;80640	chr2:178560796;178560795;178560794	chr2:179425523;179425522;179425521
N2A	25878	77857;77858;77859	chr2:178560796;178560795;178560794	chr2:179425523;179425522;179425521
N2B	19381	58366;58367;58368	chr2:178560796;178560795;178560794	chr2:179425523;179425522;179425521
Novex-1	19506	58741;58742;58743	chr2:178560796;178560795;178560794	chr2:179425523;179425522;179425521
Novex-2	19573	58942;58943;58944	chr2:178560796;178560795;178560794	chr2:179425523;179425522;179425521
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: Ig-143
• Domain position: 89
• Structural Position: 175
• Q(SASA): 0.4594
• 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	0.822	N	0.553	0.264	0.365317461125	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.5928	likely_pathogenic	0.5766	pathogenic	-0.363	Destabilizing	0.754	D	0.588	neutral	None	None	None	None	N
K/C	0.7776	likely_pathogenic	0.7491	pathogenic	-0.474	Destabilizing	0.998	D	0.76	deleterious	None	None	None	None	N
K/D	0.8468	likely_pathogenic	0.8381	pathogenic	0.035	Stabilizing	0.956	D	0.572	neutral	None	None	None	None	N
K/E	0.318	likely_benign	0.3125	benign	0.126	Stabilizing	0.822	D	0.553	neutral	N	0.485630331	None	None	N
K/F	0.8553	likely_pathogenic	0.8327	pathogenic	-0.141	Destabilizing	0.978	D	0.714	prob.delet.	None	None	None	None	N
K/G	0.8353	likely_pathogenic	0.8144	pathogenic	-0.701	Destabilizing	0.86	D	0.565	neutral	None	None	None	None	N
K/H	0.3908	ambiguous	0.3744	ambiguous	-1.022	Destabilizing	0.994	D	0.6	neutral	None	None	None	None	N
K/I	0.3463	ambiguous	0.3283	benign	0.492	Stabilizing	0.942	D	0.706	prob.neutral	N	0.487911737	None	None	N
K/L	0.4348	ambiguous	0.4056	ambiguous	0.492	Stabilizing	0.754	D	0.581	neutral	None	None	None	None	N
K/M	0.2718	likely_benign	0.2586	benign	0.262	Stabilizing	0.998	D	0.6	neutral	None	None	None	None	N
K/N	0.6911	likely_pathogenic	0.6605	pathogenic	-0.313	Destabilizing	0.942	D	0.514	neutral	N	0.484935996	None	None	N
K/P	0.9779	likely_pathogenic	0.977	pathogenic	0.238	Stabilizing	0.978	D	0.603	neutral	None	None	None	None	N
K/Q	0.2146	likely_benign	0.1992	benign	-0.373	Destabilizing	0.942	D	0.553	neutral	N	0.486693515	None	None	N
K/R	0.0909	likely_benign	0.0867	benign	-0.507	Destabilizing	0.014	N	0.253	neutral	D	0.530077954	None	None	N
K/S	0.6748	likely_pathogenic	0.6528	pathogenic	-0.921	Destabilizing	0.754	D	0.528	neutral	None	None	None	None	N
K/T	0.2389	likely_benign	0.2302	benign	-0.631	Destabilizing	0.032	N	0.383	neutral	N	0.518127377	None	None	N
K/V	0.3269	likely_benign	0.3123	benign	0.238	Stabilizing	0.915	D	0.565	neutral	None	None	None	None	N
K/W	0.8531	likely_pathogenic	0.8235	pathogenic	-0.06	Destabilizing	0.998	D	0.783	deleterious	None	None	None	None	N
K/Y	0.7364	likely_pathogenic	0.7068	pathogenic	0.239	Stabilizing	0.993	D	0.684	prob.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.