TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9917	29974;29975;29976	chr2:178704723;178704722;178704721	chr2:179569450;179569449;179569448
N2AB	9600	29023;29024;29025	chr2:178704723;178704722;178704721	chr2:179569450;179569449;179569448
N2A	8673	26242;26243;26244	chr2:178704723;178704722;178704721	chr2:179569450;179569449;179569448
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: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-84
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.1381
• 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/V	None	None	0.117	None	0.309	0.253	0.26169431596	gnomAD-4.0.0	1.20034E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31252E-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
A/C	0.9044	likely_pathogenic	0.9236	pathogenic	-1.014	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
A/D	0.9848	likely_pathogenic	0.9916	pathogenic	-1.815	Destabilizing	0.999	D	0.849	deleterious	None	None	None	None	N
A/E	0.9828	likely_pathogenic	0.9888	pathogenic	-1.727	Destabilizing	0.998	D	0.803	deleterious	None	None	None	None	N
A/F	0.9843	likely_pathogenic	0.9848	pathogenic	-0.919	Destabilizing	0.995	D	0.853	deleterious	None	None	None	None	N
A/G	0.5801	likely_pathogenic	0.6392	pathogenic	-1.504	Destabilizing	0.989	D	0.645	neutral	None	None	None	None	N
A/H	0.9917	likely_pathogenic	0.994	pathogenic	-1.845	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
A/I	0.9447	likely_pathogenic	0.9313	pathogenic	-0.122	Destabilizing	0.966	D	0.728	prob.delet.	None	None	None	None	N
A/K	0.9936	likely_pathogenic	0.996	pathogenic	-1.388	Destabilizing	0.998	D	0.807	deleterious	None	None	None	None	N
A/L	0.9215	likely_pathogenic	0.9207	pathogenic	-0.122	Destabilizing	0.966	D	0.645	neutral	None	None	None	None	N
A/M	0.9509	likely_pathogenic	0.9514	pathogenic	-0.108	Destabilizing	0.999	D	0.821	deleterious	None	None	None	None	N
A/N	0.978	likely_pathogenic	0.9867	pathogenic	-1.327	Destabilizing	0.999	D	0.853	deleterious	None	None	None	None	N
A/P	0.9798	likely_pathogenic	0.988	pathogenic	-0.407	Destabilizing	0.999	D	0.845	deleterious	None	None	None	None	N
A/Q	0.9815	likely_pathogenic	0.9872	pathogenic	-1.309	Destabilizing	0.999	D	0.839	deleterious	None	None	None	None	N
A/R	0.9761	likely_pathogenic	0.9826	pathogenic	-1.236	Destabilizing	0.998	D	0.839	deleterious	None	None	None	None	N
A/S	0.4143	ambiguous	0.5091	ambiguous	-1.743	Destabilizing	0.989	D	0.641	neutral	None	None	None	None	N
A/T	0.6474	likely_pathogenic	0.6938	pathogenic	-1.542	Destabilizing	0.977	D	0.654	neutral	None	None	None	None	N
A/V	0.7518	likely_pathogenic	0.7405	pathogenic	-0.407	Destabilizing	0.117	N	0.309	neutral	None	None	None	None	N
A/W	0.9988	likely_pathogenic	0.999	pathogenic	-1.517	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
A/Y	0.9929	likely_pathogenic	0.9936	pathogenic	-1.022	Destabilizing	0.998	D	0.859	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.