TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5172	15739;15740;15741	chr2:178733875;178733874;178733873	chr2:179598602;179598601;179598600
N2AB	4855	14788;14789;14790	chr2:178733875;178733874;178733873	chr2:179598602;179598601;179598600
N2A	3928	12007;12008;12009	chr2:178733875;178733874;178733873	chr2:179598602;179598601;179598600
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: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-35
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.5451
• 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	1.0	D	0.7	0.483	0.307648195649	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	1.94099E-04	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	0.565	likely_pathogenic	0.6115	pathogenic	-0.249	Destabilizing	0.999	D	0.661	neutral	None	None	None	None	N
K/C	0.82	likely_pathogenic	0.8544	pathogenic	-0.289	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	N
K/D	0.7607	likely_pathogenic	0.7939	pathogenic	0.158	Stabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
K/E	0.245	likely_benign	0.2841	benign	0.237	Stabilizing	0.999	D	0.628	neutral	N	0.510586158	None	None	N
K/F	0.8949	likely_pathogenic	0.9255	pathogenic	-0.007	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
K/G	0.6002	likely_pathogenic	0.6269	pathogenic	-0.574	Destabilizing	1.0	D	0.67	neutral	None	None	None	None	N
K/H	0.4197	ambiguous	0.4596	ambiguous	-0.841	Destabilizing	1.0	D	0.632	neutral	None	None	None	None	N
K/I	0.6122	likely_pathogenic	0.7038	pathogenic	0.569	Stabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
K/L	0.5555	ambiguous	0.625	pathogenic	0.569	Stabilizing	1.0	D	0.67	neutral	None	None	None	None	N
K/M	0.4153	ambiguous	0.477	ambiguous	0.312	Stabilizing	1.0	D	0.621	neutral	D	0.621298269	None	None	N
K/N	0.6045	likely_pathogenic	0.6434	pathogenic	-0.059	Destabilizing	1.0	D	0.7	prob.neutral	D	0.588100865	None	None	N
K/P	0.929	likely_pathogenic	0.9393	pathogenic	0.328	Stabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
K/Q	0.1468	likely_benign	0.1644	benign	-0.141	Destabilizing	1.0	D	0.677	prob.neutral	N	0.490099948	None	None	N
K/R	0.0827	likely_benign	0.0894	benign	-0.339	Destabilizing	0.999	D	0.557	neutral	N	0.511606496	None	None	N
K/S	0.5714	likely_pathogenic	0.6008	pathogenic	-0.659	Destabilizing	0.999	D	0.655	neutral	None	None	None	None	N
K/T	0.3001	likely_benign	0.3274	benign	-0.39	Destabilizing	1.0	D	0.698	prob.neutral	N	0.503649496	None	None	N
K/V	0.5494	ambiguous	0.6369	pathogenic	0.328	Stabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
K/W	0.838	likely_pathogenic	0.8758	pathogenic	0.073	Stabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
K/Y	0.7848	likely_pathogenic	0.8296	pathogenic	0.36	Stabilizing	1.0	D	0.672	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.