TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5241	15946;15947;15948	chr2:178733668;178733667;178733666	chr2:179598395;179598394;179598393
N2AB	4924	14995;14996;14997	chr2:178733668;178733667;178733666	chr2:179598395;179598394;179598393
N2A	3997	12214;12215;12216	chr2:178733668;178733667;178733666	chr2:179598395;179598394;179598393
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-35
• Domain position: 74
• Structural Position: 157
• Q(SASA): 0.3041
• 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
L/P	rs1448200477	None	0.989	D	0.707	0.512	0.841180832786	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/P	rs1448200477	None	0.989	D	0.707	0.512	0.841180832786	gnomAD-4.0.0	6.56944E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.46977E-05	0	0
L/Q	rs1448200477	None	0.062	N	0.501	0.296	0.613699239204	gnomAD-4.0.0	1.59264E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.41429E-04	0	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
L/A	0.1898	likely_benign	0.1927	benign	-1.731	Destabilizing	0.525	D	0.552	neutral	None	None	None	None	N
L/C	0.3777	ambiguous	0.3934	ambiguous	-1.046	Destabilizing	0.998	D	0.603	neutral	None	None	None	None	N
L/D	0.6817	likely_pathogenic	0.6853	pathogenic	-1.34	Destabilizing	0.949	D	0.697	prob.neutral	None	None	None	None	N
L/E	0.2616	likely_benign	0.272	benign	-1.361	Destabilizing	0.728	D	0.671	neutral	None	None	None	None	N
L/F	0.1003	likely_benign	0.0934	benign	-1.368	Destabilizing	0.037	N	0.348	neutral	None	None	None	None	N
L/G	0.5764	likely_pathogenic	0.5864	pathogenic	-2.032	Highly Destabilizing	0.915	D	0.696	prob.neutral	None	None	None	None	N
L/H	0.1195	likely_benign	0.1192	benign	-1.206	Destabilizing	0.993	D	0.695	prob.neutral	None	None	None	None	N
L/I	0.062	likely_benign	0.0603	benign	-0.979	Destabilizing	0.016	N	0.347	neutral	None	None	None	None	N
L/K	0.145	likely_benign	0.148	benign	-1.059	Destabilizing	0.728	D	0.661	neutral	None	None	None	None	N
L/M	0.0887	likely_benign	0.0886	benign	-0.692	Destabilizing	0.934	D	0.603	neutral	N	0.48486702	None	None	N
L/N	0.3686	ambiguous	0.3542	ambiguous	-0.844	Destabilizing	0.974	D	0.709	prob.delet.	None	None	None	None	N
L/P	0.9666	likely_pathogenic	0.9657	pathogenic	-1.2	Destabilizing	0.989	D	0.707	prob.neutral	D	0.585420739	None	None	N
L/Q	0.0926	likely_benign	0.0914	benign	-1.105	Destabilizing	0.062	N	0.501	neutral	N	0.367175513	None	None	N
L/R	0.1	likely_benign	0.1016	benign	-0.415	Destabilizing	0.934	D	0.669	neutral	N	0.42207077	None	None	N
L/S	0.2137	likely_benign	0.2132	benign	-1.45	Destabilizing	0.842	D	0.665	neutral	None	None	None	None	N
L/T	0.132	likely_benign	0.1369	benign	-1.362	Destabilizing	0.842	D	0.599	neutral	None	None	None	None	N
L/V	0.0606	likely_benign	0.0613	benign	-1.2	Destabilizing	0.012	N	0.275	neutral	N	0.445420418	None	None	N
L/W	0.1965	likely_benign	0.1943	benign	-1.393	Destabilizing	0.998	D	0.669	neutral	None	None	None	None	N
L/Y	0.2592	likely_benign	0.2553	benign	-1.171	Destabilizing	0.904	D	0.615	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.