TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6891	20896;20897;20898	chr2:178725533;178725532;178725531	chr2:179590260;179590259;179590258
N2AB	6574	19945;19946;19947	chr2:178725533;178725532;178725531	chr2:179590260;179590259;179590258
N2A	5647	17164;17165;17166	chr2:178725533;178725532;178725531	chr2:179590260;179590259;179590258
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-53
• Domain position: 38
• Structural Position: 52
• Q(SASA): 0.8115
• 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/R	None	None	0.999	N	0.593	0.167	0.213573922156	gnomAD-4.0.0	3.18539E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72145E-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	0.446	ambiguous	0.54	ambiguous	-0.006	Destabilizing	0.999	D	0.641	neutral	None	None	None	None	N
K/C	0.8847	likely_pathogenic	0.904	pathogenic	-0.266	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
K/D	0.4521	ambiguous	0.5193	ambiguous	0.024	Stabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
K/E	0.1913	likely_benign	0.2569	benign	0.066	Stabilizing	0.999	D	0.643	neutral	N	0.495937511	None	None	N
K/F	0.8792	likely_pathogenic	0.9173	pathogenic	-0.068	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
K/G	0.3096	likely_benign	0.3517	ambiguous	-0.239	Destabilizing	1.0	D	0.597	neutral	None	None	None	None	N
K/H	0.4359	ambiguous	0.4779	ambiguous	-0.382	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
K/I	0.6428	likely_pathogenic	0.7503	pathogenic	0.543	Stabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	N
K/L	0.573	likely_pathogenic	0.6716	pathogenic	0.543	Stabilizing	1.0	D	0.597	neutral	None	None	None	None	N
K/M	0.3918	ambiguous	0.5127	ambiguous	0.1	Stabilizing	1.0	D	0.66	neutral	N	0.484836733	None	None	N
K/N	0.3225	likely_benign	0.3973	ambiguous	0.14	Stabilizing	1.0	D	0.701	prob.neutral	N	0.452493378	None	None	N
K/P	0.6636	likely_pathogenic	0.7102	pathogenic	0.389	Stabilizing	1.0	D	0.667	neutral	None	None	None	None	N
K/Q	0.1733	likely_benign	0.2038	benign	0.054	Stabilizing	1.0	D	0.686	prob.neutral	N	0.46571852	None	None	N
K/R	0.0955	likely_benign	0.0984	benign	-0.01	Destabilizing	0.999	D	0.593	neutral	N	0.454108725	None	None	N
K/S	0.428	ambiguous	0.5169	ambiguous	-0.315	Destabilizing	0.999	D	0.644	neutral	None	None	None	None	N
K/T	0.2665	likely_benign	0.3545	ambiguous	-0.112	Destabilizing	1.0	D	0.654	neutral	N	0.454108725	None	None	N
K/V	0.5957	likely_pathogenic	0.7067	pathogenic	0.389	Stabilizing	1.0	D	0.654	neutral	None	None	None	None	N
K/W	0.8194	likely_pathogenic	0.8749	pathogenic	-0.11	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	N
K/Y	0.6967	likely_pathogenic	0.7659	pathogenic	0.23	Stabilizing	1.0	D	0.649	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.