TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20450	61573;61574;61575	chr2:178590377;178590376;178590375	chr2:179455104;179455103;179455102
N2AB	18809	56650;56651;56652	chr2:178590377;178590376;178590375	chr2:179455104;179455103;179455102
N2A	17882	53869;53870;53871	chr2:178590377;178590376;178590375	chr2:179455104;179455103;179455102
N2B	11385	34378;34379;34380	chr2:178590377;178590376;178590375	chr2:179455104;179455103;179455102
Novex-1	11510	34753;34754;34755	chr2:178590377;178590376;178590375	chr2:179455104;179455103;179455102
Novex-2	11577	34954;34955;34956	chr2:178590377;178590376;178590375	chr2:179455104;179455103;179455102
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-36
• Domain position: 80
• Structural Position: 111
• Q(SASA): 0.1241
• 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
A/S	None	None	0.136	N	0.396	0.152	0.158396225186	gnomAD-4.0.0	1.6623E-06	None	None	None	None	N	None	0	2.44451E-05	None	0	0	None	0	0	0	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
A/C	0.3998	ambiguous	0.3939	ambiguous	-1.367	Destabilizing	0.998	D	0.649	neutral	None	None	None	None	N
A/D	0.8873	likely_pathogenic	0.8604	pathogenic	-1.517	Destabilizing	0.934	D	0.701	prob.neutral	N	0.506995159	None	None	N
A/E	0.7114	likely_pathogenic	0.6361	pathogenic	-1.473	Destabilizing	0.842	D	0.704	prob.neutral	None	None	None	None	N
A/F	0.5603	ambiguous	0.5087	ambiguous	-0.982	Destabilizing	0.974	D	0.714	prob.delet.	None	None	None	None	N
A/G	0.3824	ambiguous	0.3733	ambiguous	-1.415	Destabilizing	0.801	D	0.61	neutral	N	0.482214144	None	None	N
A/H	0.7646	likely_pathogenic	0.7358	pathogenic	-1.422	Destabilizing	0.998	D	0.68	prob.neutral	None	None	None	None	N
A/I	0.3012	likely_benign	0.2634	benign	-0.337	Destabilizing	0.728	D	0.677	prob.neutral	None	None	None	None	N
A/K	0.7978	likely_pathogenic	0.747	pathogenic	-1.129	Destabilizing	0.842	D	0.699	prob.neutral	None	None	None	None	N
A/L	0.3378	likely_benign	0.3096	benign	-0.337	Destabilizing	0.525	D	0.638	neutral	None	None	None	None	N
A/M	0.3271	likely_benign	0.3015	benign	-0.567	Destabilizing	0.974	D	0.675	neutral	None	None	None	None	N
A/N	0.6703	likely_pathogenic	0.6546	pathogenic	-1.075	Destabilizing	0.949	D	0.697	prob.neutral	None	None	None	None	N
A/P	0.9864	likely_pathogenic	0.9878	pathogenic	-0.549	Destabilizing	0.966	D	0.695	prob.neutral	N	0.466786882	None	None	N
A/Q	0.5832	likely_pathogenic	0.5388	ambiguous	-1.164	Destabilizing	0.974	D	0.707	prob.neutral	None	None	None	None	N
A/R	0.7079	likely_pathogenic	0.6533	pathogenic	-0.924	Destabilizing	0.974	D	0.7	prob.neutral	None	None	None	None	N
A/S	0.1575	likely_benign	0.1494	benign	-1.537	Destabilizing	0.136	N	0.396	neutral	N	0.430246529	None	None	N
A/T	0.118	likely_benign	0.1097	benign	-1.385	Destabilizing	0.051	N	0.404	neutral	N	0.416431869	None	None	N
A/V	0.144	likely_benign	0.1282	benign	-0.549	Destabilizing	0.005	N	0.185	neutral	N	0.324380139	None	None	N
A/W	0.8967	likely_pathogenic	0.8801	pathogenic	-1.345	Destabilizing	0.998	D	0.756	deleterious	None	None	None	None	N
A/Y	0.7104	likely_pathogenic	0.6726	pathogenic	-0.911	Destabilizing	0.991	D	0.691	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.