TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16382	49369;49370;49371	chr2:178614253;178614252;178614251	chr2:179478980;179478979;179478978
N2AB	14741	44446;44447;44448	chr2:178614253;178614252;178614251	chr2:179478980;179478979;179478978
N2A	13814	41665;41666;41667	chr2:178614253;178614252;178614251	chr2:179478980;179478979;179478978
N2B	7317	22174;22175;22176	chr2:178614253;178614252;178614251	chr2:179478980;179478979;179478978
Novex-1	7442	22549;22550;22551	chr2:178614253;178614252;178614251	chr2:179478980;179478979;179478978
Novex-2	7509	22750;22751;22752	chr2:178614253;178614252;178614251	chr2:179478980;179478979;179478978
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: Fn3-6
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.8619
• 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
K/R	None	None	0.135	N	0.193	0.052	0.245660935333	gnomAD-4.0.0	2.73848E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.69935E-06	0	1.65854E-05

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	0.3402	ambiguous	0.293	benign	0.073	Stabilizing	0.985	D	0.587	neutral	None	None	None	None	I
K/C	0.7467	likely_pathogenic	0.6871	pathogenic	-0.159	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	I
K/D	0.5623	ambiguous	0.5153	ambiguous	-0.098	Destabilizing	0.998	D	0.532	neutral	None	None	None	None	I
K/E	0.2208	likely_benign	0.1935	benign	-0.106	Destabilizing	0.98	D	0.567	neutral	N	0.403429492	None	None	I
K/F	0.8513	likely_pathogenic	0.7891	pathogenic	-0.213	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	I
K/G	0.5218	ambiguous	0.4612	ambiguous	-0.085	Destabilizing	0.993	D	0.545	neutral	None	None	None	None	I
K/H	0.3806	ambiguous	0.3393	benign	-0.264	Destabilizing	1.0	D	0.569	neutral	None	None	None	None	I
K/I	0.4286	ambiguous	0.3795	ambiguous	0.409	Stabilizing	0.999	D	0.664	neutral	None	None	None	None	I
K/L	0.4186	ambiguous	0.3571	ambiguous	0.409	Stabilizing	0.993	D	0.537	neutral	None	None	None	None	I
K/M	0.3349	likely_benign	0.2775	benign	0.122	Stabilizing	1.0	D	0.569	neutral	N	0.481673934	None	None	I
K/N	0.4257	ambiguous	0.3902	ambiguous	0.306	Stabilizing	0.997	D	0.517	neutral	N	0.467844833	None	None	I
K/P	0.4083	ambiguous	0.3646	ambiguous	0.322	Stabilizing	0.323	N	0.375	neutral	None	None	None	None	I
K/Q	0.1646	likely_benign	0.148	benign	0.139	Stabilizing	0.994	D	0.551	neutral	N	0.479249	None	None	I
K/R	0.0869	likely_benign	0.0825	benign	0.064	Stabilizing	0.135	N	0.193	neutral	N	0.472478946	None	None	I
K/S	0.4474	ambiguous	0.3968	ambiguous	-0.101	Destabilizing	0.993	D	0.549	neutral	None	None	None	None	I
K/T	0.2184	likely_benign	0.1924	benign	0.021	Stabilizing	0.997	D	0.531	neutral	N	0.479626016	None	None	I
K/V	0.3426	ambiguous	0.3008	benign	0.322	Stabilizing	0.998	D	0.571	neutral	None	None	None	None	I
K/W	0.8662	likely_pathogenic	0.8086	pathogenic	-0.287	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	I
K/Y	0.7475	likely_pathogenic	0.6773	pathogenic	0.071	Stabilizing	0.999	D	0.649	neutral	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.