TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9558	28897;28898;28899	chr2:178709647;178709646;178709645	chr2:179574374;179574373;179574372
N2AB	9241	27946;27947;27948	chr2:178709647;178709646;178709645	chr2:179574374;179574373;179574372
N2A	8314	25165;25166;25167	chr2:178709647;178709646;178709645	chr2:179574374;179574373;179574372
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: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Ig-81
• Domain position: 66
• Structural Position: 146
• Q(SASA): 0.5584
• 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
M/I	rs868771235	None	0.028	None	0.172	0.127	0.228597637076	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
M/V	None	None	0.001	None	0.075	0.104	0.130388298395	gnomAD-4.0.0	1.59111E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85806E-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
M/A	0.2324	likely_benign	0.233	benign	-0.73	Destabilizing	0.032	N	0.231	neutral	None	None	None	None	I
M/C	0.6683	likely_pathogenic	0.6638	pathogenic	-0.567	Destabilizing	0.901	D	0.251	neutral	None	None	None	None	I
M/D	0.5556	ambiguous	0.5666	pathogenic	0.057	Stabilizing	0.148	N	0.317	neutral	None	None	None	None	I
M/E	0.2399	likely_benign	0.2346	benign	-0.001	Destabilizing	0.036	N	0.298	neutral	None	None	None	None	I
M/F	0.2558	likely_benign	0.2536	benign	-0.373	Destabilizing	0.174	N	0.19	neutral	None	None	None	None	I
M/G	0.3534	ambiguous	0.3541	ambiguous	-0.911	Destabilizing	0.148	N	0.282	neutral	None	None	None	None	I
M/H	0.3679	ambiguous	0.3737	ambiguous	-0.064	Destabilizing	0.749	D	0.335	neutral	None	None	None	None	I
M/I	0.1778	likely_benign	0.1768	benign	-0.342	Destabilizing	0.028	N	0.172	neutral	None	None	None	None	I
M/K	0.0907	likely_benign	0.0954	benign	0.252	Stabilizing	0.001	N	0.127	neutral	None	None	None	None	I
M/L	0.0952	likely_benign	0.0957	benign	-0.342	Destabilizing	None	N	0.079	neutral	None	None	None	None	I
M/N	0.2909	likely_benign	0.3083	benign	0.421	Stabilizing	0.148	N	0.359	neutral	None	None	None	None	I
M/P	0.3032	likely_benign	0.3209	benign	-0.443	Destabilizing	0.001	N	0.147	neutral	None	None	None	None	I
M/Q	0.1431	likely_benign	0.1521	benign	0.213	Stabilizing	0.002	N	0.095	neutral	None	None	None	None	I
M/R	0.0952	likely_benign	0.0936	benign	0.799	Stabilizing	0.061	N	0.282	neutral	None	None	None	None	I
M/S	0.2545	likely_benign	0.2763	benign	-0.039	Destabilizing	0.07	N	0.272	neutral	None	None	None	None	I
M/T	0.1499	likely_benign	0.1516	benign	0.001	Stabilizing	0.054	N	0.286	neutral	None	None	None	None	I
M/V	0.0786	likely_benign	0.0806	benign	-0.443	Destabilizing	0.001	N	0.075	neutral	None	None	None	None	I
M/W	0.439	ambiguous	0.4256	ambiguous	-0.308	Destabilizing	0.901	D	0.265	neutral	None	None	None	None	I
M/Y	0.4536	ambiguous	0.4581	ambiguous	-0.186	Destabilizing	0.46	N	0.335	neutral	None	None	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.