TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15583	46972;46973;46974	chr2:178618803;178618802;178618801	chr2:179483530;179483529;179483528
N2AB	13942	42049;42050;42051	chr2:178618803;178618802;178618801	chr2:179483530;179483529;179483528
N2A	13015	39268;39269;39270	chr2:178618803;178618802;178618801	chr2:179483530;179483529;179483528
N2B	6518	19777;19778;19779	chr2:178618803;178618802;178618801	chr2:179483530;179483529;179483528
Novex-1	6643	20152;20153;20154	chr2:178618803;178618802;178618801	chr2:179483530;179483529;179483528
Novex-2	6710	20353;20354;20355	chr2:178618803;178618802;178618801	chr2:179483530;179483529;179483528
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-108
• Domain position: 16
• Structural Position: 25
• Q(SASA): 0.6143
• 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/N	rs1460478978	0.207	0.22	N	0.419	0.115	0.0716867268079	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	0	0	None	0	6.60502E-04	None	0	None	0	0	0
K/N	rs1460478978	0.207	0.22	N	0.419	0.115	0.0716867268079	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	1.94856E-04	None	0	0	0	0	0
K/N	rs1460478978	0.207	0.22	N	0.419	0.115	0.0716867268079	gnomAD-4.0.0	6.58302E-06	None	None	None	None	I	None	0	0	None	0	1.94856E-04	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	0.4498	ambiguous	0.5951	pathogenic	-0.1	Destabilizing	0.157	N	0.487	neutral	None	None	None	None	I
K/C	0.6516	likely_pathogenic	0.8299	pathogenic	-0.13	Destabilizing	0.968	D	0.661	neutral	None	None	None	None	I
K/D	0.6315	likely_pathogenic	0.7591	pathogenic	0.068	Stabilizing	0.272	N	0.463	neutral	None	None	None	None	I
K/E	0.253	likely_benign	0.336	benign	0.11	Stabilizing	0.055	N	0.502	neutral	N	0.437799751	None	None	I
K/F	0.7362	likely_pathogenic	0.8397	pathogenic	-0.054	Destabilizing	0.89	D	0.613	neutral	None	None	None	None	I
K/G	0.5273	ambiguous	0.6904	pathogenic	-0.378	Destabilizing	0.272	N	0.477	neutral	None	None	None	None	I
K/H	0.283	likely_benign	0.3885	ambiguous	-0.725	Destabilizing	0.567	D	0.452	neutral	None	None	None	None	I
K/I	0.438	ambiguous	0.5717	pathogenic	0.575	Stabilizing	0.726	D	0.603	neutral	None	None	None	None	I
K/L	0.347	ambiguous	0.5083	ambiguous	0.575	Stabilizing	0.272	N	0.477	neutral	None	None	None	None	I
K/M	0.2808	likely_benign	0.4168	ambiguous	0.373	Stabilizing	0.667	D	0.453	neutral	N	0.45537372	None	None	I
K/N	0.384	ambiguous	0.4944	ambiguous	0.127	Stabilizing	0.22	N	0.419	neutral	N	0.431734083	None	None	I
K/P	0.9065	likely_pathogenic	0.9667	pathogenic	0.38	Stabilizing	0.726	D	0.423	neutral	None	None	None	None	I
K/Q	0.132	likely_benign	0.1586	benign	-0.015	Destabilizing	0.001	N	0.209	neutral	N	0.436825468	None	None	I
K/R	0.1078	likely_benign	0.1363	benign	-0.232	Destabilizing	0.124	N	0.438	neutral	N	0.452173473	None	None	I
K/S	0.4248	ambiguous	0.566	pathogenic	-0.397	Destabilizing	0.157	N	0.426	neutral	None	None	None	None	I
K/T	0.2654	likely_benign	0.3731	ambiguous	-0.186	Destabilizing	0.22	N	0.437	neutral	N	0.450707854	None	None	I
K/V	0.3989	ambiguous	0.5546	ambiguous	0.38	Stabilizing	0.567	D	0.449	neutral	None	None	None	None	I
K/W	0.776	likely_pathogenic	0.8963	pathogenic	-0.017	Destabilizing	0.968	D	0.689	prob.neutral	None	None	None	None	I
K/Y	0.5765	likely_pathogenic	0.7281	pathogenic	0.295	Stabilizing	0.726	D	0.557	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.