TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25086	75481;75482;75483	chr2:178570876;178570875;178570874	chr2:179435603;179435602;179435601
N2AB	23445	70558;70559;70560	chr2:178570876;178570875;178570874	chr2:179435603;179435602;179435601
N2A	22518	67777;67778;67779	chr2:178570876;178570875;178570874	chr2:179435603;179435602;179435601
N2B	16021	48286;48287;48288	chr2:178570876;178570875;178570874	chr2:179435603;179435602;179435601
Novex-1	16146	48661;48662;48663	chr2:178570876;178570875;178570874	chr2:179435603;179435602;179435601
Novex-2	16213	48862;48863;48864	chr2:178570876;178570875;178570874	chr2:179435603;179435602;179435601
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Fn3-70
• Domain position: 81
• Structural Position: 113
• Q(SASA): 0.6082
• 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
A/V	rs1707949011	None	0.014	N	0.304	0.312	0.284150004643	gnomAD-4.0.0	4.80129E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.25001E-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
A/C	0.8097	likely_pathogenic	0.8002	pathogenic	-0.796	Destabilizing	0.998	D	0.358	neutral	None	None	None	None	I
A/D	0.9007	likely_pathogenic	0.8913	pathogenic	-0.925	Destabilizing	0.942	D	0.608	neutral	N	0.492564424	None	None	I
A/E	0.8078	likely_pathogenic	0.7967	pathogenic	-1.072	Destabilizing	0.956	D	0.449	neutral	None	None	None	None	I
A/F	0.7735	likely_pathogenic	0.7555	pathogenic	-1.222	Destabilizing	0.956	D	0.614	neutral	None	None	None	None	I
A/G	0.3452	ambiguous	0.31	benign	-0.614	Destabilizing	0.822	D	0.391	neutral	N	0.460258607	None	None	I
A/H	0.907	likely_pathogenic	0.9005	pathogenic	-0.615	Destabilizing	0.998	D	0.622	neutral	None	None	None	None	I
A/I	0.5712	likely_pathogenic	0.5453	ambiguous	-0.534	Destabilizing	0.043	N	0.344	neutral	None	None	None	None	I
A/K	0.9366	likely_pathogenic	0.932	pathogenic	-0.666	Destabilizing	0.956	D	0.453	neutral	None	None	None	None	I
A/L	0.4759	ambiguous	0.4573	ambiguous	-0.534	Destabilizing	0.303	N	0.486	neutral	None	None	None	None	I
A/M	0.4904	ambiguous	0.469	ambiguous	-0.306	Destabilizing	0.988	D	0.477	neutral	None	None	None	None	I
A/N	0.7496	likely_pathogenic	0.7209	pathogenic	-0.385	Destabilizing	0.956	D	0.619	neutral	None	None	None	None	I
A/P	0.9517	likely_pathogenic	0.9412	pathogenic	-0.503	Destabilizing	0.99	D	0.483	neutral	N	0.472244612	None	None	I
A/Q	0.8015	likely_pathogenic	0.78	pathogenic	-0.752	Destabilizing	0.978	D	0.484	neutral	None	None	None	None	I
A/R	0.8811	likely_pathogenic	0.872	pathogenic	-0.16	Destabilizing	0.978	D	0.48	neutral	None	None	None	None	I
A/S	0.1649	likely_benign	0.1595	benign	-0.594	Destabilizing	0.294	N	0.237	neutral	N	0.501183907	None	None	I
A/T	0.2438	likely_benign	0.2201	benign	-0.674	Destabilizing	0.822	D	0.407	neutral	N	0.472089573	None	None	I
A/V	0.3253	likely_benign	0.3088	benign	-0.503	Destabilizing	0.014	N	0.304	neutral	N	0.474433431	None	None	I
A/W	0.9729	likely_pathogenic	0.968	pathogenic	-1.331	Destabilizing	0.998	D	0.697	prob.neutral	None	None	None	None	I
A/Y	0.8844	likely_pathogenic	0.8774	pathogenic	-0.966	Destabilizing	0.978	D	0.623	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.