TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28654	86185;86186;86187	chr2:178560172;178560171;178560170	chr2:179424899;179424898;179424897
N2AB	27013	81262;81263;81264	chr2:178560172;178560171;178560170	chr2:179424899;179424898;179424897
N2A	26086	78481;78482;78483	chr2:178560172;178560171;178560170	chr2:179424899;179424898;179424897
N2B	19589	58990;58991;58992	chr2:178560172;178560171;178560170	chr2:179424899;179424898;179424897
Novex-1	19714	59365;59366;59367	chr2:178560172;178560171;178560170	chr2:179424899;179424898;179424897
Novex-2	19781	59566;59567;59568	chr2:178560172;178560171;178560170	chr2:179424899;179424898;179424897
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-97
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.2398
• 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
P/L	None	None	1.0	N	0.908	0.42	0.772784792456	gnomAD-4.0.0	3.18265E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.7169E-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
P/A	0.1077	likely_benign	0.083	benign	-1.233	Destabilizing	1.0	D	0.853	deleterious	N	0.485518234	None	None	N
P/C	0.6175	likely_pathogenic	0.5395	ambiguous	-1.315	Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
P/D	0.9366	likely_pathogenic	0.9191	pathogenic	-1.997	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
P/E	0.7037	likely_pathogenic	0.6135	pathogenic	-2.048	Highly Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
P/F	0.7858	likely_pathogenic	0.7437	pathogenic	-1.394	Destabilizing	1.0	D	0.925	deleterious	None	None	None	None	N
P/G	0.6315	likely_pathogenic	0.5751	pathogenic	-1.433	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
P/H	0.5292	ambiguous	0.4714	ambiguous	-0.891	Destabilizing	1.0	D	0.896	deleterious	N	0.51402621	None	None	N
P/I	0.5907	likely_pathogenic	0.4947	ambiguous	-0.799	Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
P/K	0.6652	likely_pathogenic	0.5523	ambiguous	-0.945	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
P/L	0.3203	likely_benign	0.2713	benign	-0.799	Destabilizing	1.0	D	0.908	deleterious	N	0.520356086	None	None	N
P/M	0.5526	ambiguous	0.4775	ambiguous	-0.701	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
P/N	0.7751	likely_pathogenic	0.74	pathogenic	-0.931	Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	N
P/Q	0.3707	ambiguous	0.2953	benign	-1.278	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
P/R	0.492	ambiguous	0.3857	ambiguous	-0.381	Destabilizing	1.0	D	0.918	deleterious	N	0.501148968	None	None	N
P/S	0.2474	likely_benign	0.208	benign	-1.282	Destabilizing	1.0	D	0.871	deleterious	N	0.474384206	None	None	N
P/T	0.307	likely_benign	0.25	benign	-1.244	Destabilizing	1.0	D	0.864	deleterious	N	0.501909436	None	None	N
P/V	0.41	ambiguous	0.3206	benign	-0.913	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
P/W	0.9255	likely_pathogenic	0.9068	pathogenic	-1.486	Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
P/Y	0.7981	likely_pathogenic	0.7554	pathogenic	-1.132	Destabilizing	1.0	D	0.933	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.