TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30878	92857;92858;92859	chr2:178548994;178548993;178548992	chr2:179413721;179413720;179413719
N2AB	29237	87934;87935;87936	chr2:178548994;178548993;178548992	chr2:179413721;179413720;179413719
N2A	28310	85153;85154;85155	chr2:178548994;178548993;178548992	chr2:179413721;179413720;179413719
N2B	21813	65662;65663;65664	chr2:178548994;178548993;178548992	chr2:179413721;179413720;179413719
Novex-1	21938	66037;66038;66039	chr2:178548994;178548993;178548992	chr2:179413721;179413720;179413719
Novex-2	22005	66238;66239;66240	chr2:178548994;178548993;178548992	chr2:179413721;179413720;179413719
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: Fn3-113
• Domain position: 58
• Structural Position: 88
• Q(SASA): 0.7854
• Predicted PPI site: I

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/I	rs1279509755	0.654	0.642	N	0.422	0.242	0.386882687439	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	0	1.65618E-04

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	0.2422	likely_benign	0.2576	benign	-0.088	Destabilizing	0.001	N	0.127	neutral	None	None	None	None	I
K/C	0.5795	likely_pathogenic	0.6269	pathogenic	-0.345	Destabilizing	0.944	D	0.284	neutral	None	None	None	None	I
K/D	0.3909	ambiguous	0.4096	ambiguous	0.017	Stabilizing	0.003	N	0.142	neutral	None	None	None	None	I
K/E	0.1621	likely_benign	0.173	benign	0.074	Stabilizing	0.139	N	0.155	neutral	N	0.442135604	None	None	I
K/F	0.6612	likely_pathogenic	0.7132	pathogenic	-0.085	Destabilizing	0.543	D	0.413	neutral	None	None	None	None	I
K/G	0.3214	likely_benign	0.3249	benign	-0.339	Destabilizing	0.329	N	0.218	neutral	None	None	None	None	I
K/H	0.2224	likely_benign	0.2607	benign	-0.485	Destabilizing	0.007	N	0.169	neutral	None	None	None	None	I
K/I	0.3484	ambiguous	0.386	ambiguous	0.515	Stabilizing	0.642	D	0.422	neutral	N	0.437519218	None	None	I
K/L	0.3107	likely_benign	0.343	ambiguous	0.515	Stabilizing	0.495	N	0.227	neutral	None	None	None	None	I
K/M	0.2036	likely_benign	0.2289	benign	0.043	Stabilizing	0.981	D	0.308	neutral	None	None	None	None	I
K/N	0.2566	likely_benign	0.2707	benign	-0.02	Destabilizing	0.425	N	0.23	neutral	N	0.444847835	None	None	I
K/P	0.6559	likely_pathogenic	0.6573	pathogenic	0.343	Stabilizing	0.828	D	0.383	neutral	None	None	None	None	I
K/Q	0.1096	likely_benign	0.1173	benign	-0.068	Destabilizing	0.065	N	0.12	neutral	N	0.424339277	None	None	I
K/R	0.0833	likely_benign	0.0855	benign	-0.153	Destabilizing	0.425	N	0.275	neutral	N	0.456315622	None	None	I
K/S	0.2852	likely_benign	0.3002	benign	-0.477	Destabilizing	0.329	N	0.16	neutral	None	None	None	None	I
K/T	0.1501	likely_benign	0.158	benign	-0.253	Destabilizing	0.425	N	0.269	neutral	N	0.398304682	None	None	I
K/V	0.3002	likely_benign	0.3363	benign	0.343	Stabilizing	0.329	N	0.275	neutral	None	None	None	None	I
K/W	0.7086	likely_pathogenic	0.7577	pathogenic	-0.126	Destabilizing	0.995	D	0.28	neutral	None	None	None	None	I
K/Y	0.5072	ambiguous	0.5591	ambiguous	0.201	Stabilizing	0.013	N	0.184	neutral	None	None	None	None	I

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.