TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	950	3073;3074;3075	chr2:178783058;178783057;178783056	chr2:179647785;179647784;179647783
N2AB	950	3073;3074;3075	chr2:178783058;178783057;178783056	chr2:179647785;179647784;179647783
N2A	950	3073;3074;3075	chr2:178783058;178783057;178783056	chr2:179647785;179647784;179647783
N2B	904	2935;2936;2937	chr2:178783058;178783057;178783056	chr2:179647785;179647784;179647783
Novex-1	904	2935;2936;2937	chr2:178783058;178783057;178783056	chr2:179647785;179647784;179647783
Novex-2	904	2935;2936;2937	chr2:178783058;178783057;178783056	chr2:179647785;179647784;179647783
Novex-3	950	3073;3074;3075	chr2:178783058;178783057;178783056	chr2:179647785;179647784;179647783

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-3
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.837
• 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/E	rs367559160	0.185	0.996	N	0.566	0.554	None	gnomAD-2.1.1	2.49E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	5.44E-05	0
K/E	rs367559160	0.185	0.996	N	0.566	0.554	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	2.94E-05	0	0
K/E	rs367559160	0.185	0.996	N	0.566	0.554	None	gnomAD-4.0.0	7.68285E-05	None	None	None	None	I	None	2.66973E-05	0	None	0	0	None	0	0	1.02543E-04	0	1.60046E-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	0.6989	likely_pathogenic	0.7791	pathogenic	0.012	Stabilizing	0.998	D	0.583	neutral	None	None	None	None	I
K/C	0.9204	likely_pathogenic	0.9448	pathogenic	-0.16	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
K/D	0.848	likely_pathogenic	0.904	pathogenic	0.022	Stabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	I
K/E	0.3024	likely_benign	0.4058	ambiguous	0.035	Stabilizing	0.996	D	0.566	neutral	N	0.469206115	None	None	I
K/F	0.9729	likely_pathogenic	0.9834	pathogenic	-0.131	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	I
K/G	0.7751	likely_pathogenic	0.8417	pathogenic	-0.202	Destabilizing	1.0	D	0.537	neutral	None	None	None	None	I
K/H	0.541	ambiguous	0.6062	pathogenic	-0.473	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
K/I	0.7984	likely_pathogenic	0.8565	pathogenic	0.503	Stabilizing	1.0	D	0.723	prob.delet.	N	0.519784907	None	None	I
K/L	0.7381	likely_pathogenic	0.8102	pathogenic	0.503	Stabilizing	1.0	D	0.537	neutral	None	None	None	None	I
K/M	0.6064	likely_pathogenic	0.7088	pathogenic	0.229	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
K/N	0.6815	likely_pathogenic	0.7708	pathogenic	0.243	Stabilizing	0.999	D	0.693	prob.neutral	N	0.514020567	None	None	I
K/P	0.936	likely_pathogenic	0.9627	pathogenic	0.367	Stabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
K/Q	0.182	likely_benign	0.2145	benign	0.08	Stabilizing	0.999	D	0.685	prob.neutral	N	0.437186345	None	None	I
K/R	0.1095	likely_benign	0.1148	benign	-0.057	Destabilizing	0.64	D	0.266	neutral	N	0.455562619	None	None	I
K/S	0.672	likely_pathogenic	0.757	pathogenic	-0.223	Destabilizing	0.998	D	0.625	neutral	None	None	None	None	I
K/T	0.4302	ambiguous	0.5159	ambiguous	-0.06	Destabilizing	0.999	D	0.66	neutral	N	0.50296553	None	None	I
K/V	0.7452	likely_pathogenic	0.8093	pathogenic	0.367	Stabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	I
K/W	0.9518	likely_pathogenic	0.9693	pathogenic	-0.148	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
K/Y	0.9154	likely_pathogenic	0.9463	pathogenic	0.195	Stabilizing	1.0	D	0.699	prob.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.