TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33574	100945;100946;100947	chr2:178536027;178536026;178536025	chr2:179400754;179400753;179400752
N2AB	31933	96022;96023;96024	chr2:178536027;178536026;178536025	chr2:179400754;179400753;179400752
N2A	31006	93241;93242;93243	chr2:178536027;178536026;178536025	chr2:179400754;179400753;179400752
N2B	24509	73750;73751;73752	chr2:178536027;178536026;178536025	chr2:179400754;179400753;179400752
Novex-1	24634	74125;74126;74127	chr2:178536027;178536026;178536025	chr2:179400754;179400753;179400752
Novex-2	24701	74326;74327;74328	chr2:178536027;178536026;178536025	chr2:179400754;179400753;179400752
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-158
• Domain position: 79
• Structural Position: 161
• Q(SASA): 0.0862
• 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
N/S	rs1691356141	None	0.879	D	0.525	0.624	0.357313475932	gnomAD-4.0.0	3.40251E-06	None	None	None	None	I	None	0	0	None	0	2.80222E-05	None	0	0	0	1.61155E-05	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
N/A	0.9952	likely_pathogenic	0.9906	pathogenic	-0.535	Destabilizing	0.754	D	0.677	prob.neutral	None	None	None	None	I
N/C	0.9342	likely_pathogenic	0.9202	pathogenic	-0.056	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
N/D	0.9956	likely_pathogenic	0.9895	pathogenic	-1.448	Destabilizing	0.935	D	0.595	neutral	D	0.641824087	None	None	I
N/E	0.9992	likely_pathogenic	0.9982	pathogenic	-1.389	Destabilizing	0.984	D	0.652	neutral	None	None	None	None	I
N/F	0.9991	likely_pathogenic	0.9985	pathogenic	-0.676	Destabilizing	0.999	D	0.764	deleterious	None	None	None	None	I
N/G	0.9904	likely_pathogenic	0.9805	pathogenic	-0.804	Destabilizing	0.994	D	0.54	neutral	None	None	None	None	I
N/H	0.9811	likely_pathogenic	0.9632	pathogenic	-0.767	Destabilizing	0.999	D	0.697	prob.neutral	D	0.643236717	None	None	I
N/I	0.9948	likely_pathogenic	0.9892	pathogenic	0.119	Stabilizing	0.996	D	0.764	deleterious	D	0.617900409	None	None	I
N/K	0.9994	likely_pathogenic	0.9985	pathogenic	-0.152	Destabilizing	0.994	D	0.659	neutral	D	0.642631304	None	None	I
N/L	0.9876	likely_pathogenic	0.9781	pathogenic	0.119	Stabilizing	0.994	D	0.753	deleterious	None	None	None	None	I
N/M	0.9963	likely_pathogenic	0.9929	pathogenic	0.696	Stabilizing	1.0	D	0.75	deleterious	None	None	None	None	I
N/P	0.998	likely_pathogenic	0.9961	pathogenic	-0.071	Destabilizing	0.993	D	0.738	prob.delet.	None	None	None	None	I
N/Q	0.9986	likely_pathogenic	0.9966	pathogenic	-1.065	Destabilizing	0.998	D	0.705	prob.neutral	None	None	None	None	I
N/R	0.998	likely_pathogenic	0.9956	pathogenic	-0.016	Destabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	I
N/S	0.7925	likely_pathogenic	0.7163	pathogenic	-0.72	Destabilizing	0.879	D	0.525	neutral	D	0.55766976	None	None	I
N/T	0.9692	likely_pathogenic	0.9406	pathogenic	-0.509	Destabilizing	0.065	N	0.317	neutral	D	0.609956809	None	None	I
N/V	0.9915	likely_pathogenic	0.9857	pathogenic	-0.071	Destabilizing	0.928	D	0.755	deleterious	None	None	None	None	I
N/W	0.9997	likely_pathogenic	0.9994	pathogenic	-0.558	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
N/Y	0.9927	likely_pathogenic	0.9874	pathogenic	-0.229	Destabilizing	1.0	D	0.757	deleterious	D	0.617900409	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.