TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22237	66934;66935;66936	chr2:178581559;178581558;178581557	chr2:179446286;179446285;179446284
N2AB	20596	62011;62012;62013	chr2:178581559;178581558;178581557	chr2:179446286;179446285;179446284
N2A	19669	59230;59231;59232	chr2:178581559;178581558;178581557	chr2:179446286;179446285;179446284
N2B	13172	39739;39740;39741	chr2:178581559;178581558;178581557	chr2:179446286;179446285;179446284
Novex-1	13297	40114;40115;40116	chr2:178581559;178581558;178581557	chr2:179446286;179446285;179446284
Novex-2	13364	40315;40316;40317	chr2:178581559;178581558;178581557	chr2:179446286;179446285;179446284
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-49
• Domain position: 82
• Structural Position: 113
• Q(SASA): 0.5928
• 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/N	None	None	0.988	N	0.603	0.271	0.201204373187	gnomAD-4.0.0	1.59508E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86546E-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	0.3489	ambiguous	0.3629	ambiguous	-0.098	Destabilizing	0.968	D	0.557	neutral	None	None	None	None	I
K/C	0.7523	likely_pathogenic	0.7526	pathogenic	-0.363	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
K/D	0.5797	likely_pathogenic	0.5923	pathogenic	0.205	Stabilizing	0.991	D	0.547	neutral	None	None	None	None	I
K/E	0.2018	likely_benign	0.2114	benign	0.229	Stabilizing	0.919	D	0.45	neutral	N	0.45443011	None	None	I
K/F	0.8985	likely_pathogenic	0.9001	pathogenic	-0.266	Destabilizing	1.0	D	0.627	neutral	None	None	None	None	I
K/G	0.5406	ambiguous	0.5425	ambiguous	-0.312	Destabilizing	0.991	D	0.477	neutral	None	None	None	None	I
K/H	0.3799	ambiguous	0.3812	ambiguous	-0.545	Destabilizing	0.999	D	0.597	neutral	None	None	None	None	I
K/I	0.4599	ambiguous	0.4727	ambiguous	0.388	Stabilizing	0.995	D	0.633	neutral	None	None	None	None	I
K/L	0.5022	ambiguous	0.5158	ambiguous	0.388	Stabilizing	0.991	D	0.477	neutral	None	None	None	None	I
K/M	0.3385	likely_benign	0.3507	ambiguous	0.139	Stabilizing	0.998	D	0.598	neutral	D	0.523772765	None	None	I
K/N	0.4838	ambiguous	0.4871	ambiguous	0.089	Stabilizing	0.988	D	0.603	neutral	N	0.511611545	None	None	I
K/P	0.7545	likely_pathogenic	0.724	pathogenic	0.255	Stabilizing	0.995	D	0.601	neutral	None	None	None	None	I
K/Q	0.1432	likely_benign	0.1437	benign	-0.046	Destabilizing	0.414	N	0.325	neutral	N	0.506763085	None	None	I
K/R	0.0919	likely_benign	0.0903	benign	-0.074	Destabilizing	0.919	D	0.452	neutral	N	0.472458511	None	None	I
K/S	0.4313	ambiguous	0.4389	ambiguous	-0.452	Destabilizing	0.968	D	0.542	neutral	None	None	None	None	I
K/T	0.2249	likely_benign	0.2299	benign	-0.265	Destabilizing	0.988	D	0.548	neutral	N	0.509744675	None	None	I
K/V	0.4001	ambiguous	0.4169	ambiguous	0.255	Stabilizing	0.991	D	0.575	neutral	None	None	None	None	I
K/W	0.9006	likely_pathogenic	0.8983	pathogenic	-0.258	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	I
K/Y	0.7794	likely_pathogenic	0.7843	pathogenic	0.09	Stabilizing	0.998	D	0.621	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.