TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23442	70549;70550;70551	chr2:178575808;178575807;178575806	chr2:179440535;179440534;179440533
N2AB	21801	65626;65627;65628	chr2:178575808;178575807;178575806	chr2:179440535;179440534;179440533
N2A	20874	62845;62846;62847	chr2:178575808;178575807;178575806	chr2:179440535;179440534;179440533
N2B	14377	43354;43355;43356	chr2:178575808;178575807;178575806	chr2:179440535;179440534;179440533
Novex-1	14502	43729;43730;43731	chr2:178575808;178575807;178575806	chr2:179440535;179440534;179440533
Novex-2	14569	43930;43931;43932	chr2:178575808;178575807;178575806	chr2:179440535;179440534;179440533
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Fn3-58
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.1885
• 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
L/M	rs1553614105	None	0.949	N	0.645	0.355	0.568785453283	gnomAD-4.0.0	1.36897E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79969E-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
L/A	0.9417	likely_pathogenic	0.9565	pathogenic	-2.456	Highly Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
L/C	0.8528	likely_pathogenic	0.8887	pathogenic	-1.757	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
L/D	0.999	likely_pathogenic	0.9993	pathogenic	-2.709	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
L/E	0.9946	likely_pathogenic	0.9961	pathogenic	-2.565	Highly Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
L/F	0.3619	ambiguous	0.5159	ambiguous	-1.525	Destabilizing	0.999	D	0.835	deleterious	None	None	None	None	N
L/G	0.9881	likely_pathogenic	0.9916	pathogenic	-2.942	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
L/H	0.9743	likely_pathogenic	0.9841	pathogenic	-2.382	Highly Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
L/I	0.133	likely_benign	0.1502	benign	-1.087	Destabilizing	0.937	D	0.731	prob.delet.	None	None	None	None	N
L/K	0.9879	likely_pathogenic	0.9907	pathogenic	-1.909	Destabilizing	0.995	D	0.853	deleterious	None	None	None	None	N
L/M	0.2884	likely_benign	0.331	benign	-0.967	Destabilizing	0.949	D	0.645	neutral	N	0.516328205	None	None	N
L/N	0.9905	likely_pathogenic	0.9933	pathogenic	-2.011	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
L/P	0.9408	likely_pathogenic	0.9604	pathogenic	-1.521	Destabilizing	1.0	D	0.869	deleterious	D	0.527186791	None	None	N
L/Q	0.9735	likely_pathogenic	0.9814	pathogenic	-2.007	Highly Destabilizing	1.0	D	0.867	deleterious	D	0.540219358	None	None	N
L/R	0.978	likely_pathogenic	0.9836	pathogenic	-1.484	Destabilizing	1.0	D	0.861	deleterious	D	0.540219358	None	None	N
L/S	0.9876	likely_pathogenic	0.9916	pathogenic	-2.664	Highly Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
L/T	0.9187	likely_pathogenic	0.9347	pathogenic	-2.389	Highly Destabilizing	0.999	D	0.821	deleterious	None	None	None	None	N
L/V	0.1729	likely_benign	0.196	benign	-1.521	Destabilizing	0.282	N	0.483	neutral	N	0.473906879	None	None	N
L/W	0.912	likely_pathogenic	0.9476	pathogenic	-1.866	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
L/Y	0.9271	likely_pathogenic	0.9581	pathogenic	-1.615	Destabilizing	0.999	D	0.819	deleterious	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.