TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33387	100384;100385;100386	chr2:178536950;178536949;178536948	chr2:179401677;179401676;179401675
N2AB	31746	95461;95462;95463	chr2:178536950;178536949;178536948	chr2:179401677;179401676;179401675
N2A	30819	92680;92681;92682	chr2:178536950;178536949;178536948	chr2:179401677;179401676;179401675
N2B	24322	73189;73190;73191	chr2:178536950;178536949;178536948	chr2:179401677;179401676;179401675
Novex-1	24447	73564;73565;73566	chr2:178536950;178536949;178536948	chr2:179401677;179401676;179401675
Novex-2	24514	73765;73766;73767	chr2:178536950;178536949;178536948	chr2:179401677;179401676;179401675
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-130
• Domain position: 98
• Structural Position: 131
• Q(SASA): 0.6367
• 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
K/N	None	None	0.974	N	0.662	0.311	0.181679512989	gnomAD-4.0.0	1.37387E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80554E-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
K/A	0.7207	likely_pathogenic	0.7214	pathogenic	-0.329	Destabilizing	0.933	D	0.576	neutral	None	None	None	None	N
K/C	0.8888	likely_pathogenic	0.8783	pathogenic	-0.42	Destabilizing	0.999	D	0.835	deleterious	None	None	None	None	N
K/D	0.8684	likely_pathogenic	0.8844	pathogenic	0.132	Stabilizing	0.99	D	0.707	prob.delet.	None	None	None	None	N
K/E	0.4647	ambiguous	0.4808	ambiguous	0.227	Stabilizing	0.914	D	0.523	neutral	N	0.459685494	None	None	N
K/F	0.9699	likely_pathogenic	0.9693	pathogenic	-0.021	Destabilizing	0.999	D	0.81	deleterious	None	None	None	None	N
K/G	0.805	likely_pathogenic	0.8141	pathogenic	-0.677	Destabilizing	0.98	D	0.596	neutral	None	None	None	None	N
K/H	0.5237	ambiguous	0.5248	ambiguous	-0.973	Destabilizing	0.997	D	0.703	prob.delet.	None	None	None	None	N
K/I	0.8154	likely_pathogenic	0.8055	pathogenic	0.555	Stabilizing	0.99	D	0.825	deleterious	None	None	None	None	N
K/L	0.8073	likely_pathogenic	0.7961	pathogenic	0.555	Stabilizing	0.98	D	0.596	neutral	None	None	None	None	N
K/M	0.7202	likely_pathogenic	0.697	pathogenic	0.308	Stabilizing	0.999	D	0.704	prob.delet.	N	0.471730271	None	None	N
K/N	0.7434	likely_pathogenic	0.7453	pathogenic	-0.197	Destabilizing	0.974	D	0.662	prob.neutral	N	0.486872011	None	None	N
K/P	0.9308	likely_pathogenic	0.9528	pathogenic	0.291	Stabilizing	0.997	D	0.709	prob.delet.	None	None	None	None	N
K/Q	0.2384	likely_benign	0.2283	benign	-0.269	Destabilizing	0.974	D	0.689	prob.delet.	N	0.49498308	None	None	N
K/R	0.1162	likely_benign	0.1109	benign	-0.454	Destabilizing	0.071	N	0.259	neutral	N	0.489462617	None	None	N
K/S	0.7153	likely_pathogenic	0.7158	pathogenic	-0.832	Destabilizing	0.933	D	0.635	neutral	None	None	None	None	N
K/T	0.4369	ambiguous	0.4244	ambiguous	-0.538	Destabilizing	0.974	D	0.656	prob.neutral	N	0.487499747	None	None	N
K/V	0.7652	likely_pathogenic	0.7598	pathogenic	0.291	Stabilizing	0.99	D	0.77	deleterious	None	None	None	None	N
K/W	0.9616	likely_pathogenic	0.9636	pathogenic	0.087	Stabilizing	0.999	D	0.847	deleterious	None	None	None	None	N
K/Y	0.9208	likely_pathogenic	0.919	pathogenic	0.371	Stabilizing	0.997	D	0.801	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.