TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19084	57475;57476;57477	chr2:178597920;178597919;178597918	chr2:179462647;179462646;179462645
N2AB	17443	52552;52553;52554	chr2:178597920;178597919;178597918	chr2:179462647;179462646;179462645
N2A	16516	49771;49772;49773	chr2:178597920;178597919;178597918	chr2:179462647;179462646;179462645
N2B	10019	30280;30281;30282	chr2:178597920;178597919;178597918	chr2:179462647;179462646;179462645
Novex-1	10144	30655;30656;30657	chr2:178597920;178597919;178597918	chr2:179462647;179462646;179462645
Novex-2	10211	30856;30857;30858	chr2:178597920;178597919;178597918	chr2:179462647;179462646;179462645
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: Fn3-26
• Domain position: 97
• Structural Position: 131
• Q(SASA): 0.4773
• 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/T	rs1445268725	-0.662	0.986	N	0.681	0.401	0.32714864917	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
K/T	rs1445268725	-0.662	0.986	N	0.681	0.401	0.32714864917	gnomAD-4.0.0	1.59256E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43394E-05	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	0.5397	ambiguous	0.5976	pathogenic	-0.574	Destabilizing	0.963	D	0.521	neutral	None	None	None	None	N
K/C	0.7632	likely_pathogenic	0.7897	pathogenic	-0.483	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
K/D	0.8215	likely_pathogenic	0.8544	pathogenic	-0.352	Destabilizing	0.929	D	0.655	prob.neutral	None	None	None	None	N
K/E	0.2754	likely_benign	0.313	benign	-0.229	Destabilizing	0.058	N	0.211	neutral	N	0.494230931	None	None	N
K/F	0.9068	likely_pathogenic	0.9259	pathogenic	-0.169	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
K/G	0.6922	likely_pathogenic	0.7347	pathogenic	-0.964	Destabilizing	0.989	D	0.585	neutral	None	None	None	None	N
K/H	0.4148	ambiguous	0.4443	ambiguous	-1.369	Destabilizing	0.999	D	0.628	neutral	None	None	None	None	N
K/I	0.5461	ambiguous	0.5661	pathogenic	0.447	Stabilizing	0.995	D	0.805	deleterious	None	None	None	None	N
K/L	0.5853	likely_pathogenic	0.6339	pathogenic	0.447	Stabilizing	0.989	D	0.604	neutral	None	None	None	None	N
K/M	0.3798	ambiguous	0.4169	ambiguous	0.331	Stabilizing	0.999	D	0.637	neutral	N	0.462184391	None	None	N
K/N	0.5921	likely_pathogenic	0.6372	pathogenic	-0.566	Destabilizing	0.986	D	0.674	prob.neutral	N	0.488682437	None	None	N
K/P	0.9704	likely_pathogenic	0.9742	pathogenic	0.137	Stabilizing	0.995	D	0.689	prob.delet.	None	None	None	None	N
K/Q	0.1611	likely_benign	0.1791	benign	-0.582	Destabilizing	0.972	D	0.695	prob.delet.	N	0.460156475	None	None	N
K/R	0.0939	likely_benign	0.097	benign	-0.769	Destabilizing	0.952	D	0.586	neutral	N	0.463873526	None	None	N
K/S	0.6268	likely_pathogenic	0.6796	pathogenic	-1.138	Destabilizing	0.963	D	0.595	neutral	None	None	None	None	N
K/T	0.2675	likely_benign	0.2947	benign	-0.805	Destabilizing	0.986	D	0.681	prob.neutral	N	0.467348951	None	None	N
K/V	0.4557	ambiguous	0.4836	ambiguous	0.137	Stabilizing	0.995	D	0.71	prob.delet.	None	None	None	None	N
K/W	0.884	likely_pathogenic	0.9057	pathogenic	-0.086	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
K/Y	0.846	likely_pathogenic	0.8681	pathogenic	0.187	Stabilizing	0.998	D	0.739	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.