TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8420	25483;25484;25485	chr2:178717616;178717615;178717614	chr2:179582343;179582342;179582341
N2AB	8103	24532;24533;24534	chr2:178717616;178717615;178717614	chr2:179582343;179582342;179582341
N2A	7176	21751;21752;21753	chr2:178717616;178717615;178717614	chr2:179582343;179582342;179582341
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: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-69
• Domain position: 61
• Structural Position: 141
• Q(SASA): 0.403
• 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/S	None	None	0.918	N	0.38	0.196	0.764019764511	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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	0.2374	likely_benign	0.2508	benign	-1.252	Destabilizing	0.924	D	0.337	neutral	None	None	None	None	N
L/C	0.5913	likely_pathogenic	0.5559	ambiguous	-0.661	Destabilizing	1.0	D	0.386	neutral	None	None	None	None	N
L/D	0.6524	likely_pathogenic	0.6702	pathogenic	-0.793	Destabilizing	0.937	D	0.431	neutral	None	None	None	None	N
L/E	0.3241	likely_benign	0.3346	benign	-0.866	Destabilizing	0.226	N	0.297	neutral	None	None	None	None	N
L/F	0.1119	likely_benign	0.1156	benign	-1.068	Destabilizing	0.984	D	0.353	neutral	D	0.525997499	None	None	N
L/G	0.4598	ambiguous	0.4692	ambiguous	-1.487	Destabilizing	0.984	D	0.424	neutral	None	None	None	None	N
L/H	0.1793	likely_benign	0.1787	benign	-0.697	Destabilizing	0.082	N	0.387	neutral	None	None	None	None	N
L/I	0.0979	likely_benign	0.0998	benign	-0.721	Destabilizing	0.396	N	0.251	neutral	D	0.53273147	None	None	N
L/K	0.2061	likely_benign	0.2072	benign	-0.748	Destabilizing	0.303	N	0.369	neutral	None	None	None	None	N
L/M	0.1183	likely_benign	0.1194	benign	-0.456	Destabilizing	0.987	D	0.387	neutral	None	None	None	None	N
L/N	0.3461	ambiguous	0.357	ambiguous	-0.442	Destabilizing	0.967	D	0.437	neutral	None	None	None	None	N
L/P	0.4021	ambiguous	0.3965	ambiguous	-0.866	Destabilizing	0.085	N	0.348	neutral	None	None	None	None	N
L/Q	0.114	likely_benign	0.1158	benign	-0.735	Destabilizing	0.323	N	0.312	neutral	None	None	None	None	N
L/R	0.1359	likely_benign	0.1324	benign	-0.069	Destabilizing	0.922	D	0.409	neutral	None	None	None	None	N
L/S	0.2084	likely_benign	0.2216	benign	-0.958	Destabilizing	0.918	D	0.38	neutral	N	0.498077392	None	None	N
L/T	0.1994	likely_benign	0.2052	benign	-0.928	Destabilizing	0.106	N	0.179	neutral	None	None	None	None	N
L/V	0.108	likely_benign	0.1087	benign	-0.866	Destabilizing	0.263	N	0.255	neutral	D	0.527440294	None	None	N
L/W	0.1961	likely_benign	0.1859	benign	-1.057	Destabilizing	1.0	D	0.432	neutral	None	None	None	None	N
L/Y	0.2924	likely_benign	0.2951	benign	-0.845	Destabilizing	0.828	D	0.398	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.