TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15881	47866;47867;47868	chr2:178617444;178617443;178617442	chr2:179482171;179482170;179482169
N2AB	14240	42943;42944;42945	chr2:178617444;178617443;178617442	chr2:179482171;179482170;179482169
N2A	13313	40162;40163;40164	chr2:178617444;178617443;178617442	chr2:179482171;179482170;179482169
N2B	6816	20671;20672;20673	chr2:178617444;178617443;178617442	chr2:179482171;179482170;179482169
Novex-1	6941	21046;21047;21048	chr2:178617444;178617443;178617442	chr2:179482171;179482170;179482169
Novex-2	7008	21247;21248;21249	chr2:178617444;178617443;178617442	chr2:179482171;179482170;179482169
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-3
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.2391
• 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
E/K	rs1437852479	None	0.999	N	0.567	0.425	0.29527378943	gnomAD-3.1.2	6.59E-06	None	None	None	None	I	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs1437852479	None	0.999	N	0.567	0.425	0.29527378943	gnomAD-4.0.0	6.58718E-06	None	None	None	None	I	None	2.41815E-05	0	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
E/A	0.2328	likely_benign	0.2618	benign	-0.815	Destabilizing	0.999	D	0.713	prob.delet.	N	0.479721929	None	None	I
E/C	0.866	likely_pathogenic	0.8841	pathogenic	-0.566	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	I
E/D	0.1701	likely_benign	0.2168	benign	-1.005	Destabilizing	0.999	D	0.463	neutral	N	0.483932486	None	None	I
E/F	0.786	likely_pathogenic	0.8181	pathogenic	-0.219	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	I
E/G	0.2234	likely_benign	0.2555	benign	-1.16	Destabilizing	1.0	D	0.747	deleterious	N	0.471705947	None	None	I
E/H	0.5913	likely_pathogenic	0.6429	pathogenic	-0.387	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	I
E/I	0.4289	ambiguous	0.4738	ambiguous	0.125	Stabilizing	1.0	D	0.832	deleterious	None	None	None	None	I
E/K	0.2509	likely_benign	0.2928	benign	-0.772	Destabilizing	0.999	D	0.567	neutral	N	0.474175948	None	None	I
E/L	0.4316	ambiguous	0.5006	ambiguous	0.125	Stabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
E/M	0.4805	ambiguous	0.519	ambiguous	0.427	Stabilizing	1.0	D	0.801	deleterious	None	None	None	None	I
E/N	0.2945	likely_benign	0.3707	ambiguous	-1.17	Destabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	I
E/P	0.9706	likely_pathogenic	0.9693	pathogenic	-0.167	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
E/Q	0.1826	likely_benign	0.1958	benign	-1.029	Destabilizing	1.0	D	0.621	neutral	N	0.483932486	None	None	I
E/R	0.4362	ambiguous	0.4555	ambiguous	-0.387	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	I
E/S	0.2632	likely_benign	0.302	benign	-1.458	Destabilizing	0.999	D	0.636	neutral	None	None	None	None	I
E/T	0.2974	likely_benign	0.3262	benign	-1.18	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
E/V	0.2885	likely_benign	0.3133	benign	-0.167	Destabilizing	1.0	D	0.783	deleterious	N	0.479646859	None	None	I
E/W	0.9342	likely_pathogenic	0.9408	pathogenic	0.017	Stabilizing	1.0	D	0.837	deleterious	None	None	None	None	I
E/Y	0.6863	likely_pathogenic	0.7288	pathogenic	0.001	Stabilizing	1.0	D	0.814	deleterious	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.