TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18740	56443;56444;56445	chr2:178599683;178599682;178599681	chr2:179464410;179464409;179464408
N2AB	17099	51520;51521;51522	chr2:178599683;178599682;178599681	chr2:179464410;179464409;179464408
N2A	16172	48739;48740;48741	chr2:178599683;178599682;178599681	chr2:179464410;179464409;179464408
N2B	9675	29248;29249;29250	chr2:178599683;178599682;178599681	chr2:179464410;179464409;179464408
Novex-1	9800	29623;29624;29625	chr2:178599683;178599682;178599681	chr2:179464410;179464409;179464408
Novex-2	9867	29824;29825;29826	chr2:178599683;178599682;178599681	chr2:179464410;179464409;179464408
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-116
• Domain position: 53
• Structural Position: 123
• Q(SASA): 0.7377
• 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	None	None	1.0	N	0.677	0.315	0.214338557667	gnomAD-4.0.0	1.59287E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86123E-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	0.7685	likely_pathogenic	0.7678	pathogenic	-1.194	Destabilizing	0.999	D	0.63	neutral	None	None	None	None	I
K/C	0.8235	likely_pathogenic	0.8257	pathogenic	-1.037	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
K/D	0.9243	likely_pathogenic	0.9331	pathogenic	-1.106	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	I
K/E	0.485	ambiguous	0.5014	ambiguous	-0.885	Destabilizing	0.999	D	0.57	neutral	N	0.493423721	None	None	I
K/F	0.9389	likely_pathogenic	0.9265	pathogenic	-0.473	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	I
K/G	0.8694	likely_pathogenic	0.8734	pathogenic	-1.627	Destabilizing	1.0	D	0.623	neutral	None	None	None	None	I
K/H	0.5478	ambiguous	0.5488	ambiguous	-1.513	Destabilizing	1.0	D	0.642	neutral	None	None	None	None	I
K/I	0.6204	likely_pathogenic	0.5877	pathogenic	0.001	Stabilizing	1.0	D	0.654	neutral	N	0.458460211	None	None	I
K/L	0.6302	likely_pathogenic	0.6092	pathogenic	0.001	Stabilizing	1.0	D	0.623	neutral	None	None	None	None	I
K/M	0.4512	ambiguous	0.4283	ambiguous	-0.261	Destabilizing	1.0	D	0.641	neutral	None	None	None	None	I
K/N	0.8223	likely_pathogenic	0.8354	pathogenic	-1.294	Destabilizing	1.0	D	0.677	prob.neutral	N	0.516588582	None	None	I
K/P	0.946	likely_pathogenic	0.9517	pathogenic	-0.373	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	I
K/Q	0.2662	likely_benign	0.2835	benign	-1.115	Destabilizing	1.0	D	0.665	neutral	N	0.484900238	None	None	I
K/R	0.1297	likely_benign	0.1299	benign	-0.898	Destabilizing	0.999	D	0.566	neutral	N	0.490556774	None	None	I
K/S	0.8186	likely_pathogenic	0.8235	pathogenic	-1.868	Destabilizing	0.999	D	0.628	neutral	None	None	None	None	I
K/T	0.4183	ambiguous	0.4134	ambiguous	-1.412	Destabilizing	1.0	D	0.673	neutral	N	0.488516546	None	None	I
K/V	0.5613	ambiguous	0.5388	ambiguous	-0.373	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	I
K/W	0.9347	likely_pathogenic	0.9231	pathogenic	-0.413	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
K/Y	0.8186	likely_pathogenic	0.793	pathogenic	-0.188	Destabilizing	1.0	D	0.628	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.