TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19540	58843;58844;58845	chr2:178593682;178593681;178593680	chr2:179458409;179458408;179458407
N2AB	17899	53920;53921;53922	chr2:178593682;178593681;178593680	chr2:179458409;179458408;179458407
N2A	16972	51139;51140;51141	chr2:178593682;178593681;178593680	chr2:179458409;179458408;179458407
N2B	10475	31648;31649;31650	chr2:178593682;178593681;178593680	chr2:179458409;179458408;179458407
Novex-1	10600	32023;32024;32025	chr2:178593682;178593681;178593680	chr2:179458409;179458408;179458407
Novex-2	10667	32224;32225;32226	chr2:178593682;178593681;178593680	chr2:179458409;179458408;179458407
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-29
• Domain position: 62
• Structural Position: 92
• Q(SASA): 0.5793
• 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/I	rs2050741869	None	1.0	N	0.812	0.339	0.574056412462	gnomAD-4.0.0	1.59229E-06	None	None	None	None	N	None	0	0	None	0	2.7835E-05	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
K/A	0.7532	likely_pathogenic	0.7499	pathogenic	-0.414	Destabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	N
K/C	0.8693	likely_pathogenic	0.8577	pathogenic	-0.579	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
K/D	0.9188	likely_pathogenic	0.9284	pathogenic	-0.002	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
K/E	0.5499	ambiguous	0.5603	ambiguous	0.103	Stabilizing	0.999	D	0.608	neutral	N	0.499778398	None	None	N
K/F	0.9247	likely_pathogenic	0.9254	pathogenic	-0.162	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
K/G	0.8666	likely_pathogenic	0.8796	pathogenic	-0.749	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
K/H	0.5009	ambiguous	0.4922	ambiguous	-0.937	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
K/I	0.624	likely_pathogenic	0.6042	pathogenic	0.437	Stabilizing	1.0	D	0.812	deleterious	N	0.465924281	None	None	N
K/L	0.6562	likely_pathogenic	0.6347	pathogenic	0.437	Stabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
K/M	0.5159	ambiguous	0.5031	ambiguous	0.09	Stabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
K/N	0.8253	likely_pathogenic	0.8328	pathogenic	-0.417	Destabilizing	1.0	D	0.745	deleterious	N	0.513497056	None	None	N
K/P	0.8804	likely_pathogenic	0.881	pathogenic	0.183	Stabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
K/Q	0.3352	likely_benign	0.3233	benign	-0.43	Destabilizing	1.0	D	0.727	prob.delet.	N	0.505416291	None	None	N
K/R	0.0848	likely_benign	0.0814	benign	-0.442	Destabilizing	0.999	D	0.583	neutral	N	0.437345859	None	None	N
K/S	0.8189	likely_pathogenic	0.8212	pathogenic	-1.003	Destabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	N
K/T	0.4462	ambiguous	0.4469	ambiguous	-0.696	Destabilizing	1.0	D	0.772	deleterious	N	0.424968421	None	None	N
K/V	0.5809	likely_pathogenic	0.5472	ambiguous	0.183	Stabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
K/W	0.8892	likely_pathogenic	0.8884	pathogenic	-0.099	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
K/Y	0.8207	likely_pathogenic	0.8299	pathogenic	0.196	Stabilizing	1.0	D	0.788	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.