TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15302	46129;46130;46131	chr2:178620617;178620616;178620615	chr2:179485344;179485343;179485342
N2AB	13661	41206;41207;41208	chr2:178620617;178620616;178620615	chr2:179485344;179485343;179485342
N2A	12734	38425;38426;38427	chr2:178620617;178620616;178620615	chr2:179485344;179485343;179485342
N2B	6237	18934;18935;18936	chr2:178620617;178620616;178620615	chr2:179485344;179485343;179485342
Novex-1	6362	19309;19310;19311	chr2:178620617;178620616;178620615	chr2:179485344;179485343;179485342
Novex-2	6429	19510;19511;19512	chr2:178620617;178620616;178620615	chr2:179485344;179485343;179485342
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-105
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.379
• 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	rs1229771826	None	1.0	D	0.649	0.416	0.735594876934	gnomAD-3.1.2	6.59E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/F	rs1229771826	None	1.0	D	0.649	0.416	0.735594876934	gnomAD-4.0.0	1.24573E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.69868E-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	0.6155	likely_pathogenic	0.6119	pathogenic	-1.591	Destabilizing	0.999	D	0.62	neutral	None	None	None	None	N
L/C	0.7843	likely_pathogenic	0.7874	pathogenic	-0.987	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	N
L/D	0.9194	likely_pathogenic	0.9155	pathogenic	-1.02	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
L/E	0.7534	likely_pathogenic	0.7535	pathogenic	-1.032	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
L/F	0.456	ambiguous	0.3891	ambiguous	-1.17	Destabilizing	1.0	D	0.649	neutral	D	0.570420335	None	None	N
L/G	0.8485	likely_pathogenic	0.8496	pathogenic	-1.903	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
L/H	0.7564	likely_pathogenic	0.7231	pathogenic	-1.1	Destabilizing	1.0	D	0.729	prob.delet.	D	0.573257311	None	None	N
L/I	0.1761	likely_benign	0.1566	benign	-0.816	Destabilizing	0.999	D	0.515	neutral	N	0.49335802	None	None	N
L/K	0.706	likely_pathogenic	0.7022	pathogenic	-1.114	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
L/M	0.2651	likely_benign	0.2399	benign	-0.633	Destabilizing	1.0	D	0.6	neutral	None	None	None	None	N
L/N	0.7622	likely_pathogenic	0.7586	pathogenic	-0.888	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
L/P	0.6068	likely_pathogenic	0.6065	pathogenic	-1.042	Destabilizing	1.0	D	0.749	deleterious	D	0.573257311	None	None	N
L/Q	0.6069	likely_pathogenic	0.5919	pathogenic	-1.078	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
L/R	0.6436	likely_pathogenic	0.637	pathogenic	-0.494	Destabilizing	1.0	D	0.76	deleterious	D	0.572233192	None	None	N
L/S	0.7292	likely_pathogenic	0.6829	pathogenic	-1.482	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
L/T	0.4788	ambiguous	0.4747	ambiguous	-1.374	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
L/V	0.1876	likely_benign	0.1856	benign	-1.042	Destabilizing	0.999	D	0.557	neutral	N	0.488228951	None	None	N
L/W	0.6894	likely_pathogenic	0.6266	pathogenic	-1.217	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
L/Y	0.7566	likely_pathogenic	0.7336	pathogenic	-1.005	Destabilizing	1.0	D	0.679	prob.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.