TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	64	415;416;417	chr2:178802243;178802242;178802241	chr2:179666970;179666969;179666968
N2AB	64	415;416;417	chr2:178802243;178802242;178802241	chr2:179666970;179666969;179666968
N2A	64	415;416;417	chr2:178802243;178802242;178802241	chr2:179666970;179666969;179666968
N2B	64	415;416;417	chr2:178802243;178802242;178802241	chr2:179666970;179666969;179666968
Novex-1	64	415;416;417	chr2:178802243;178802242;178802241	chr2:179666970;179666969;179666968
Novex-2	64	415;416;417	chr2:178802243;178802242;178802241	chr2:179666970;179666969;179666968
Novex-3	64	415;416;417	chr2:178802243;178802242;178802241	chr2:179666970;179666969;179666968

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-1
• Domain position: 59
• Structural Position: 137
• Q(SASA): 0.2051
• 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/I	None	None	0.001	N	0.515	0.232	0.20549828249	gnomAD-4.0.0	1.59049E-06	None	None	None	-0.354(TCAP)	N	None	0	0	None	0	0	None	0	0	0	0	3.02151E-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	0.3274	likely_benign	0.3768	ambiguous	-1.102	Destabilizing	0.037	N	0.397	neutral	None	None	None	-0.249(TCAP)	N
K/C	0.6605	likely_pathogenic	0.7107	pathogenic	-1.276	Destabilizing	0.946	D	0.609	neutral	None	None	None	-0.145(TCAP)	N
K/D	0.7739	likely_pathogenic	0.8039	pathogenic	-1.067	Destabilizing	0.177	N	0.493	neutral	None	None	None	0.1(TCAP)	N
K/E	0.236	likely_benign	0.2572	benign	-0.875	Destabilizing	0.01	N	0.429	neutral	N	0.469217228	None	0.018(TCAP)	N
K/F	0.6643	likely_pathogenic	0.7248	pathogenic	-0.629	Destabilizing	0.378	N	0.603	neutral	None	None	None	-0.034(TCAP)	N
K/G	0.4767	ambiguous	0.5334	ambiguous	-1.533	Destabilizing	0.177	N	0.564	neutral	None	None	None	-0.223(TCAP)	N
K/H	0.2477	likely_benign	0.2873	benign	-1.805	Destabilizing	0.388	N	0.578	neutral	None	None	None	0.249(TCAP)	N
K/I	0.2331	likely_benign	0.2503	benign	0.064	Stabilizing	0.001	N	0.515	neutral	N	0.489424891	None	-0.354(TCAP)	N
K/L	0.2742	likely_benign	0.3075	benign	0.064	Stabilizing	0.001	N	0.481	neutral	None	None	None	-0.354(TCAP)	N
K/M	0.1864	likely_benign	0.2059	benign	-0.099	Destabilizing	0.154	N	0.573	neutral	None	None	None	0.171(TCAP)	N
K/N	0.5065	ambiguous	0.5514	ambiguous	-1.216	Destabilizing	0.14	N	0.391	neutral	N	0.491486757	None	-0.522(TCAP)	N
K/P	0.976	likely_pathogenic	0.9791	pathogenic	-0.298	Destabilizing	0.304	N	0.547	neutral	None	None	None	-0.315(TCAP)	N
K/Q	0.1044	likely_benign	0.1198	benign	-1.166	Destabilizing	0.01	N	0.449	neutral	N	0.489136921	None	-0.375(TCAP)	N
K/R	0.0656	likely_benign	0.0704	benign	-0.926	Destabilizing	None	N	0.193	neutral	N	0.452408785	None	-0.875(TCAP)	N
K/S	0.3789	ambiguous	0.4423	ambiguous	-1.864	Destabilizing	0.043	N	0.395	neutral	None	None	None	-0.4(TCAP)	N
K/T	0.1291	likely_benign	0.1504	benign	-1.435	Destabilizing	None	N	0.292	neutral	N	0.358649071	None	-0.444(TCAP)	N
K/V	0.2216	likely_benign	0.2465	benign	-0.298	Destabilizing	None	N	0.449	neutral	None	None	None	-0.315(TCAP)	N
K/W	0.601	likely_pathogenic	0.6914	pathogenic	-0.545	Destabilizing	0.963	D	0.642	neutral	None	None	None	0.077(TCAP)	N
K/Y	0.5649	likely_pathogenic	0.6133	pathogenic	-0.205	Destabilizing	0.067	N	0.613	neutral	None	None	None	0.077(TCAP)	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.