TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18761	56506;56507;56508	chr2:178599620;178599619;178599618	chr2:179464347;179464346;179464345
N2AB	17120	51583;51584;51585	chr2:178599620;178599619;178599618	chr2:179464347;179464346;179464345
N2A	16193	48802;48803;48804	chr2:178599620;178599619;178599618	chr2:179464347;179464346;179464345
N2B	9696	29311;29312;29313	chr2:178599620;178599619;178599618	chr2:179464347;179464346;179464345
Novex-1	9821	29686;29687;29688	chr2:178599620;178599619;178599618	chr2:179464347;179464346;179464345
Novex-2	9888	29887;29888;29889	chr2:178599620;178599619;178599618	chr2:179464347;179464346;179464345
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-116
• Domain position: 74
• Structural Position: 153
• Q(SASA): 0.2711
• 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
L/V	None	None	0.835	N	0.449	0.085	0.52122689477	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
L/A	0.3677	ambiguous	0.3638	ambiguous	-2.53	Highly Destabilizing	0.97	D	0.613	neutral	None	None	None	None	N
L/C	0.4801	ambiguous	0.4863	ambiguous	-1.783	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
L/D	0.7484	likely_pathogenic	0.7519	pathogenic	-2.816	Highly Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	N
L/E	0.4901	ambiguous	0.4798	ambiguous	-2.658	Highly Destabilizing	0.999	D	0.76	deleterious	None	None	None	None	N
L/F	0.1618	likely_benign	0.163	benign	-1.472	Destabilizing	0.989	D	0.637	neutral	N	0.515588504	None	None	N
L/G	0.6762	likely_pathogenic	0.6837	pathogenic	-2.998	Highly Destabilizing	0.996	D	0.756	deleterious	None	None	None	None	N
L/H	0.279	likely_benign	0.2801	benign	-2.345	Highly Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
L/I	0.0882	likely_benign	0.0882	benign	-1.203	Destabilizing	0.248	N	0.23	neutral	N	0.451075666	None	None	N
L/K	0.3413	ambiguous	0.3343	benign	-1.888	Destabilizing	0.996	D	0.733	prob.delet.	None	None	None	None	N
L/M	0.1285	likely_benign	0.1297	benign	-1.148	Destabilizing	0.871	D	0.401	neutral	None	None	None	None	N
L/N	0.402	ambiguous	0.3969	ambiguous	-2.04	Highly Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	N
L/P	0.6347	likely_pathogenic	0.7175	pathogenic	-1.625	Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	N
L/Q	0.2215	likely_benign	0.2147	benign	-2.024	Highly Destabilizing	0.996	D	0.741	deleterious	None	None	None	None	N
L/R	0.2698	likely_benign	0.2677	benign	-1.458	Destabilizing	0.996	D	0.739	prob.delet.	None	None	None	None	N
L/S	0.3846	ambiguous	0.3923	ambiguous	-2.684	Highly Destabilizing	0.994	D	0.698	prob.neutral	N	0.494191725	None	None	N
L/T	0.2552	likely_benign	0.2461	benign	-2.406	Highly Destabilizing	0.996	D	0.659	neutral	None	None	None	None	N
L/V	0.1077	likely_benign	0.1063	benign	-1.625	Destabilizing	0.835	D	0.449	neutral	N	0.442629541	None	None	N
L/W	0.3102	likely_benign	0.3233	benign	-1.803	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
L/Y	0.3525	ambiguous	0.3591	ambiguous	-1.588	Destabilizing	0.999	D	0.717	prob.delet.	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.