TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27146	81661;81662;81663	chr2:178564696;178564695;178564694	chr2:179429423;179429422;179429421
N2AB	25505	76738;76739;76740	chr2:178564696;178564695;178564694	chr2:179429423;179429422;179429421
N2A	24578	73957;73958;73959	chr2:178564696;178564695;178564694	chr2:179429423;179429422;179429421
N2B	18081	54466;54467;54468	chr2:178564696;178564695;178564694	chr2:179429423;179429422;179429421
Novex-1	18206	54841;54842;54843	chr2:178564696;178564695;178564694	chr2:179429423;179429422;179429421
Novex-2	18273	55042;55043;55044	chr2:178564696;178564695;178564694	chr2:179429423;179429422;179429421
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: Fn3-85
• Domain position: 75
• Structural Position: 107
• Q(SASA): 0.1036
• 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
K/N	None	None	0.117	N	0.581	0.088	0.132336055621	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.7497	likely_pathogenic	0.6637	pathogenic	-1.401	Destabilizing	0.067	N	0.592	neutral	None	None	None	None	N
K/C	0.584	likely_pathogenic	0.5455	ambiguous	-1.353	Destabilizing	0.935	D	0.761	deleterious	None	None	None	None	N
K/D	0.9774	likely_pathogenic	0.9635	pathogenic	-1.683	Destabilizing	0.149	N	0.563	neutral	None	None	None	None	N
K/E	0.6746	likely_pathogenic	0.5726	pathogenic	-1.397	Destabilizing	0.027	N	0.617	neutral	N	0.495564657	None	None	N
K/F	0.9127	likely_pathogenic	0.8819	pathogenic	-0.669	Destabilizing	0.555	D	0.731	prob.delet.	None	None	None	None	N
K/G	0.8685	likely_pathogenic	0.8075	pathogenic	-1.865	Destabilizing	0.149	N	0.59	neutral	None	None	None	None	N
K/H	0.4123	ambiguous	0.3606	ambiguous	-1.928	Destabilizing	0.555	D	0.63	neutral	None	None	None	None	N
K/I	0.5751	likely_pathogenic	0.5178	ambiguous	-0.089	Destabilizing	0.484	N	0.699	prob.neutral	N	0.486870603	None	None	N
K/L	0.6014	likely_pathogenic	0.5122	ambiguous	-0.089	Destabilizing	0.149	N	0.59	neutral	None	None	None	None	N
K/M	0.4282	ambiguous	0.3608	ambiguous	-0.496	Destabilizing	0.791	D	0.632	neutral	None	None	None	None	N
K/N	0.9029	likely_pathogenic	0.8495	pathogenic	-1.573	Destabilizing	0.117	N	0.581	neutral	N	0.515633285	None	None	N
K/P	0.9954	likely_pathogenic	0.9922	pathogenic	-0.506	Destabilizing	0.555	D	0.591	neutral	None	None	None	None	N
K/Q	0.213	likely_benign	0.1804	benign	-1.236	Destabilizing	0.117	N	0.618	neutral	N	0.427302224	None	None	N
K/R	0.0506	likely_benign	0.0497	benign	-0.958	Destabilizing	None	N	0.247	neutral	N	0.277573201	None	None	N
K/S	0.8446	likely_pathogenic	0.7772	pathogenic	-2.093	Highly Destabilizing	0.149	N	0.601	neutral	None	None	None	None	N
K/T	0.553	ambiguous	0.4649	ambiguous	-1.56	Destabilizing	0.117	N	0.564	neutral	N	0.441943603	None	None	N
K/V	0.5488	ambiguous	0.493	ambiguous	-0.506	Destabilizing	0.149	N	0.61	neutral	None	None	None	None	N
K/W	0.8317	likely_pathogenic	0.7886	pathogenic	-0.752	Destabilizing	0.935	D	0.784	deleterious	None	None	None	None	N
K/Y	0.8011	likely_pathogenic	0.7624	pathogenic	-0.38	Destabilizing	0.555	D	0.683	prob.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.