TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26663	80212;80213;80214	chr2:178566145;178566144;178566143	chr2:179430872;179430871;179430870
N2AB	25022	75289;75290;75291	chr2:178566145;178566144;178566143	chr2:179430872;179430871;179430870
N2A	24095	72508;72509;72510	chr2:178566145;178566144;178566143	chr2:179430872;179430871;179430870
N2B	17598	53017;53018;53019	chr2:178566145;178566144;178566143	chr2:179430872;179430871;179430870
Novex-1	17723	53392;53393;53394	chr2:178566145;178566144;178566143	chr2:179430872;179430871;179430870
Novex-2	17790	53593;53594;53595	chr2:178566145;178566144;178566143	chr2:179430872;179430871;179430870
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-138
• Domain position: 70
• Structural Position: 156
• Q(SASA): 0.0839
• 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/F	None	None	1.0	N	0.837	0.299	0.468253365638	gnomAD-4.0.0	5.47419E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.29675E-06	0	1.65695E-05

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	0.9039	likely_pathogenic	0.8873	pathogenic	-2.506	Highly Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	N
L/C	0.8129	likely_pathogenic	0.7959	pathogenic	-1.808	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
L/D	0.9998	likely_pathogenic	0.9997	pathogenic	-2.568	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
L/E	0.9979	likely_pathogenic	0.9974	pathogenic	-2.331	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
L/F	0.7607	likely_pathogenic	0.6906	pathogenic	-1.523	Destabilizing	1.0	D	0.837	deleterious	N	0.478253367	None	None	N
L/G	0.987	likely_pathogenic	0.9851	pathogenic	-3.077	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
L/H	0.9947	likely_pathogenic	0.9932	pathogenic	-2.508	Highly Destabilizing	1.0	D	0.827	deleterious	N	0.502486915	None	None	N
L/I	0.1604	likely_benign	0.1439	benign	-0.859	Destabilizing	0.999	D	0.713	prob.delet.	N	0.489531614	None	None	N
L/K	0.9966	likely_pathogenic	0.9961	pathogenic	-1.907	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
L/M	0.3383	likely_benign	0.3049	benign	-0.785	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
L/N	0.9975	likely_pathogenic	0.9972	pathogenic	-2.265	Highly Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
L/P	0.9977	likely_pathogenic	0.9968	pathogenic	-1.388	Destabilizing	1.0	D	0.869	deleterious	N	0.502486915	None	None	N
L/Q	0.9879	likely_pathogenic	0.9848	pathogenic	-2.094	Highly Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
L/R	0.9916	likely_pathogenic	0.9905	pathogenic	-1.674	Destabilizing	1.0	D	0.867	deleterious	N	0.502486915	None	None	N
L/S	0.9901	likely_pathogenic	0.988	pathogenic	-3.021	Highly Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
L/T	0.953	likely_pathogenic	0.9437	pathogenic	-2.622	Highly Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
L/V	0.1447	likely_benign	0.1337	benign	-1.388	Destabilizing	0.999	D	0.736	prob.delet.	N	0.45382153	None	None	N
L/W	0.9837	likely_pathogenic	0.9797	pathogenic	-1.886	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
L/Y	0.9864	likely_pathogenic	0.983	pathogenic	-1.585	Destabilizing	1.0	D	0.841	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.