TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34137	102634;102635;102636	chr2:178534206;178534205;178534204	chr2:179398933;179398932;179398931
N2AB	32496	97711;97712;97713	chr2:178534206;178534205;178534204	chr2:179398933;179398932;179398931
N2A	31569	94930;94931;94932	chr2:178534206;178534205;178534204	chr2:179398933;179398932;179398931
N2B	25072	75439;75440;75441	chr2:178534206;178534205;178534204	chr2:179398933;179398932;179398931
Novex-1	25197	75814;75815;75816	chr2:178534206;178534205;178534204	chr2:179398933;179398932;179398931
Novex-2	25264	76015;76016;76017	chr2:178534206;178534205;178534204	chr2:179398933;179398932;179398931
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-160
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.1441
• 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
P/L	None	None	0.104	N	0.404	0.236	0.516827169674	gnomAD-4.0.0	1.59096E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43271E-05	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
P/A	0.4067	ambiguous	0.4262	ambiguous	-1.823	Destabilizing	0.994	D	0.474	neutral	N	0.475064459	None	None	N
P/C	0.9499	likely_pathogenic	0.944	pathogenic	-1.582	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
P/D	0.9432	likely_pathogenic	0.9378	pathogenic	-2.628	Highly Destabilizing	1.0	D	0.585	neutral	None	None	None	None	N
P/E	0.8554	likely_pathogenic	0.86	pathogenic	-2.58	Highly Destabilizing	1.0	D	0.547	neutral	None	None	None	None	N
P/F	0.9618	likely_pathogenic	0.9638	pathogenic	-1.375	Destabilizing	0.998	D	0.682	prob.neutral	None	None	None	None	N
P/G	0.8996	likely_pathogenic	0.8791	pathogenic	-2.173	Highly Destabilizing	1.0	D	0.571	neutral	None	None	None	None	N
P/H	0.8229	likely_pathogenic	0.8285	pathogenic	-1.705	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	N
P/I	0.8286	likely_pathogenic	0.8556	pathogenic	-0.921	Destabilizing	0.983	D	0.585	neutral	None	None	None	None	N
P/K	0.8652	likely_pathogenic	0.872	pathogenic	-1.522	Destabilizing	1.0	D	0.547	neutral	None	None	None	None	N
P/L	0.5562	ambiguous	0.6339	pathogenic	-0.921	Destabilizing	0.104	N	0.404	neutral	N	0.427195942	None	None	N
P/M	0.8593	likely_pathogenic	0.8804	pathogenic	-0.894	Destabilizing	0.998	D	0.645	neutral	None	None	None	None	N
P/N	0.9094	likely_pathogenic	0.8921	pathogenic	-1.558	Destabilizing	1.0	D	0.632	neutral	None	None	None	None	N
P/Q	0.7564	likely_pathogenic	0.7788	pathogenic	-1.722	Destabilizing	0.999	D	0.593	neutral	N	0.475411176	None	None	N
P/R	0.7522	likely_pathogenic	0.7579	pathogenic	-1.029	Destabilizing	0.999	D	0.633	neutral	N	0.475411176	None	None	N
P/S	0.7022	likely_pathogenic	0.7027	pathogenic	-2.015	Highly Destabilizing	0.999	D	0.546	neutral	N	0.474717743	None	None	N
P/T	0.5891	likely_pathogenic	0.6216	pathogenic	-1.864	Destabilizing	0.994	D	0.535	neutral	N	0.475584534	None	None	N
P/V	0.7194	likely_pathogenic	0.7366	pathogenic	-1.192	Destabilizing	0.983	D	0.522	neutral	None	None	None	None	N
P/W	0.9865	likely_pathogenic	0.9867	pathogenic	-1.666	Destabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
P/Y	0.9611	likely_pathogenic	0.9545	pathogenic	-1.36	Destabilizing	1.0	D	0.681	prob.neutral	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.