TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33293	100102;100103;100104	chr2:178537232;178537231;178537230	chr2:179401959;179401958;179401957
N2AB	31652	95179;95180;95181	chr2:178537232;178537231;178537230	chr2:179401959;179401958;179401957
N2A	30725	92398;92399;92400	chr2:178537232;178537231;178537230	chr2:179401959;179401958;179401957
N2B	24228	72907;72908;72909	chr2:178537232;178537231;178537230	chr2:179401959;179401958;179401957
Novex-1	24353	73282;73283;73284	chr2:178537232;178537231;178537230	chr2:179401959;179401958;179401957
Novex-2	24420	73483;73484;73485	chr2:178537232;178537231;178537230	chr2:179401959;179401958;179401957
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: Fn3-130
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.4058
• 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/E	None	None	0.959	N	0.489	0.247	0.323886383625	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
K/I	None	None	0.061	N	0.36	0.187	0.455722563999	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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	0.2625	likely_benign	0.3164	benign	-0.622	Destabilizing	0.863	D	0.463	neutral	None	None	None	None	I
K/C	0.5855	likely_pathogenic	0.6458	pathogenic	-0.706	Destabilizing	0.999	D	0.633	neutral	None	None	None	None	I
K/D	0.7556	likely_pathogenic	0.8235	pathogenic	-0.503	Destabilizing	0.969	D	0.593	neutral	None	None	None	None	I
K/E	0.2147	likely_benign	0.2444	benign	-0.399	Destabilizing	0.959	D	0.489	neutral	N	0.466582618	None	None	I
K/F	0.6997	likely_pathogenic	0.7827	pathogenic	-0.345	Destabilizing	0.982	D	0.664	neutral	None	None	None	None	I
K/G	0.5123	ambiguous	0.5904	pathogenic	-0.991	Destabilizing	0.969	D	0.632	neutral	None	None	None	None	I
K/H	0.4193	ambiguous	0.4828	ambiguous	-1.411	Destabilizing	0.999	D	0.571	neutral	None	None	None	None	I
K/I	0.1975	likely_benign	0.2523	benign	0.336	Stabilizing	0.061	N	0.36	neutral	N	0.461532228	None	None	I
K/L	0.2988	likely_benign	0.3799	ambiguous	0.336	Stabilizing	0.02	N	0.321	neutral	None	None	None	None	I
K/M	0.168	likely_benign	0.2078	benign	0.301	Stabilizing	0.982	D	0.576	neutral	None	None	None	None	I
K/N	0.4798	ambiguous	0.576	pathogenic	-0.7	Destabilizing	0.959	D	0.475	neutral	N	0.468103555	None	None	I
K/P	0.5099	ambiguous	0.5608	ambiguous	0.047	Stabilizing	0.997	D	0.593	neutral	None	None	None	None	I
K/Q	0.1429	likely_benign	0.1512	benign	-0.81	Destabilizing	0.996	D	0.493	neutral	N	0.489601477	None	None	I
K/R	0.0888	likely_benign	0.0971	benign	-0.818	Destabilizing	0.959	D	0.511	neutral	N	0.449544365	None	None	I
K/S	0.4014	ambiguous	0.4809	ambiguous	-1.311	Destabilizing	0.884	D	0.451	neutral	None	None	None	None	I
K/T	0.1387	likely_benign	0.1969	benign	-1.005	Destabilizing	0.134	N	0.285	neutral	N	0.468650201	None	None	I
K/V	0.2122	likely_benign	0.2656	benign	0.047	Stabilizing	0.759	D	0.419	neutral	None	None	None	None	I
K/W	0.854	likely_pathogenic	0.9003	pathogenic	-0.234	Destabilizing	0.999	D	0.657	neutral	None	None	None	None	I
K/Y	0.6307	likely_pathogenic	0.7058	pathogenic	0.073	Stabilizing	0.997	D	0.646	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.