TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25049	75370;75371;75372	chr2:178570987;178570986;178570985	chr2:179435714;179435713;179435712
N2AB	23408	70447;70448;70449	chr2:178570987;178570986;178570985	chr2:179435714;179435713;179435712
N2A	22481	67666;67667;67668	chr2:178570987;178570986;178570985	chr2:179435714;179435713;179435712
N2B	15984	48175;48176;48177	chr2:178570987;178570986;178570985	chr2:179435714;179435713;179435712
Novex-1	16109	48550;48551;48552	chr2:178570987;178570986;178570985	chr2:179435714;179435713;179435712
Novex-2	16176	48751;48752;48753	chr2:178570987;178570986;178570985	chr2:179435714;179435713;179435712
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: Fn3-70
• Domain position: 44
• Structural Position: 54
• Q(SASA): 0.5693
• 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/S	rs1268559382	None	0.616	N	0.413	0.208	0.1749357433	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
P/S	rs1268559382	None	0.616	N	0.413	0.208	0.1749357433	gnomAD-4.0.0	6.57938E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47115E-05	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	0.2751	likely_benign	0.2387	benign	-0.397	Destabilizing	0.01	N	0.304	neutral	N	0.457803197	None	None	N
P/C	0.8588	likely_pathogenic	0.826	pathogenic	-0.845	Destabilizing	0.991	D	0.622	neutral	None	None	None	None	N
P/D	0.724	likely_pathogenic	0.6706	pathogenic	-0.49	Destabilizing	0.968	D	0.452	neutral	None	None	None	None	N
P/E	0.5947	likely_pathogenic	0.5329	ambiguous	-0.6	Destabilizing	0.937	D	0.41	neutral	None	None	None	None	N
P/F	0.8834	likely_pathogenic	0.852	pathogenic	-0.698	Destabilizing	0.991	D	0.611	neutral	None	None	None	None	N
P/G	0.4595	ambiguous	0.4173	ambiguous	-0.474	Destabilizing	0.68	D	0.421	neutral	None	None	None	None	N
P/H	0.5981	likely_pathogenic	0.5422	ambiguous	0.016	Stabilizing	0.996	D	0.551	neutral	N	0.453397482	None	None	N
P/I	0.7717	likely_pathogenic	0.7235	pathogenic	-0.336	Destabilizing	0.937	D	0.611	neutral	None	None	None	None	N
P/K	0.6913	likely_pathogenic	0.6519	pathogenic	-0.501	Destabilizing	0.937	D	0.419	neutral	None	None	None	None	N
P/L	0.3921	ambiguous	0.3404	ambiguous	-0.336	Destabilizing	0.849	D	0.509	neutral	N	0.456044055	None	None	N
P/M	0.701	likely_pathogenic	0.6416	pathogenic	-0.627	Destabilizing	0.997	D	0.552	neutral	None	None	None	None	N
P/N	0.6812	likely_pathogenic	0.63	pathogenic	-0.333	Destabilizing	0.968	D	0.54	neutral	None	None	None	None	N
P/Q	0.5163	ambiguous	0.4584	ambiguous	-0.551	Destabilizing	0.968	D	0.481	neutral	None	None	None	None	N
P/R	0.5531	ambiguous	0.5053	ambiguous	-0.004	Destabilizing	0.958	D	0.539	neutral	N	0.487606029	None	None	N
P/S	0.3851	ambiguous	0.3374	benign	-0.629	Destabilizing	0.616	D	0.413	neutral	N	0.469806915	None	None	N
P/T	0.3184	likely_benign	0.2742	benign	-0.648	Destabilizing	0.762	D	0.405	neutral	N	0.487432671	None	None	N
P/V	0.6162	likely_pathogenic	0.5599	ambiguous	-0.327	Destabilizing	0.68	D	0.411	neutral	None	None	None	None	N
P/W	0.914	likely_pathogenic	0.887	pathogenic	-0.755	Destabilizing	0.997	D	0.691	prob.neutral	None	None	None	None	N
P/Y	0.8457	likely_pathogenic	0.8059	pathogenic	-0.489	Destabilizing	0.997	D	0.617	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.