TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16765	50518;50519;50520	chr2:178612118;178612117;178612116	chr2:179476845;179476844;179476843
N2AB	15124	45595;45596;45597	chr2:178612118;178612117;178612116	chr2:179476845;179476844;179476843
N2A	14197	42814;42815;42816	chr2:178612118;178612117;178612116	chr2:179476845;179476844;179476843
N2B	7700	23323;23324;23325	chr2:178612118;178612117;178612116	chr2:179476845;179476844;179476843
Novex-1	7825	23698;23699;23700	chr2:178612118;178612117;178612116	chr2:179476845;179476844;179476843
Novex-2	7892	23899;23900;23901	chr2:178612118;178612117;178612116	chr2:179476845;179476844;179476843
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: Fn3-10
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.4933
• 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/Q	rs1173417812	None	1.0	N	0.729	0.361	0.276065633971	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/Q	rs1173417812	None	1.0	N	0.729	0.361	0.276065633971	gnomAD-4.0.0	2.03025E-06	None	None	None	None	N	None	3.49589E-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
K/A	0.7518	likely_pathogenic	0.7808	pathogenic	-0.288	Destabilizing	0.999	D	0.631	neutral	None	None	None	None	N
K/C	0.9408	likely_pathogenic	0.9211	pathogenic	-0.385	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
K/D	0.9142	likely_pathogenic	0.934	pathogenic	-0.207	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
K/E	0.6242	likely_pathogenic	0.681	pathogenic	-0.158	Destabilizing	0.999	D	0.585	neutral	N	0.475548586	None	None	N
K/F	0.9843	likely_pathogenic	0.9844	pathogenic	-0.223	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
K/G	0.7968	likely_pathogenic	0.8179	pathogenic	-0.588	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	N
K/H	0.7332	likely_pathogenic	0.738	pathogenic	-1.009	Destabilizing	1.0	D	0.623	neutral	None	None	None	None	N
K/I	0.8901	likely_pathogenic	0.9069	pathogenic	0.453	Stabilizing	1.0	D	0.714	prob.delet.	D	0.542839954	None	None	N
K/L	0.8055	likely_pathogenic	0.8306	pathogenic	0.453	Stabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	N
K/M	0.7654	likely_pathogenic	0.7869	pathogenic	0.376	Stabilizing	1.0	D	0.618	neutral	None	None	None	None	N
K/N	0.8576	likely_pathogenic	0.8774	pathogenic	-0.216	Destabilizing	1.0	D	0.739	prob.delet.	N	0.463395093	None	None	N
K/P	0.8055	likely_pathogenic	0.8229	pathogenic	0.236	Stabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	N
K/Q	0.3824	ambiguous	0.4117	ambiguous	-0.405	Destabilizing	1.0	D	0.729	prob.delet.	N	0.471622872	None	None	N
K/R	0.1087	likely_benign	0.1096	benign	-0.458	Destabilizing	0.999	D	0.534	neutral	N	0.473500229	None	None	N
K/S	0.7742	likely_pathogenic	0.8038	pathogenic	-0.768	Destabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	N
K/T	0.6635	likely_pathogenic	0.6985	pathogenic	-0.545	Destabilizing	1.0	D	0.708	prob.delet.	D	0.536397241	None	None	N
K/V	0.8345	likely_pathogenic	0.8488	pathogenic	0.236	Stabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
K/W	0.9696	likely_pathogenic	0.9702	pathogenic	-0.132	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
K/Y	0.949	likely_pathogenic	0.9492	pathogenic	0.18	Stabilizing	1.0	D	0.689	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.