TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27588	82987;82988;82989	chr2:178563370;178563369;178563368	chr2:179428097;179428096;179428095
N2AB	25947	78064;78065;78066	chr2:178563370;178563369;178563368	chr2:179428097;179428096;179428095
N2A	25020	75283;75284;75285	chr2:178563370;178563369;178563368	chr2:179428097;179428096;179428095
N2B	18523	55792;55793;55794	chr2:178563370;178563369;178563368	chr2:179428097;179428096;179428095
Novex-1	18648	56167;56168;56169	chr2:178563370;178563369;178563368	chr2:179428097;179428096;179428095
Novex-2	18715	56368;56369;56370	chr2:178563370;178563369;178563368	chr2:179428097;179428096;179428095
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Fn3-89
• Domain position: 19
• Structural Position: 21
• Q(SASA): 0.1605
• 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
S/F	None	None	0.994	N	0.714	0.425	0.628150982837	gnomAD-4.0.0	4.80129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.25001E-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
S/A	0.1398	likely_benign	0.1279	benign	-0.763	Destabilizing	0.773	D	0.531	neutral	N	0.468268139	None	None	N
S/C	0.1655	likely_benign	0.1507	benign	-0.821	Destabilizing	0.999	D	0.694	prob.neutral	N	0.495464202	None	None	N
S/D	0.7442	likely_pathogenic	0.7068	pathogenic	-1.172	Destabilizing	0.033	N	0.432	neutral	None	None	None	None	N
S/E	0.7885	likely_pathogenic	0.7704	pathogenic	-1.147	Destabilizing	0.845	D	0.541	neutral	None	None	None	None	N
S/F	0.3299	likely_benign	0.2719	benign	-1.11	Destabilizing	0.994	D	0.714	prob.delet.	N	0.468294593	None	None	N
S/G	0.2494	likely_benign	0.2279	benign	-1.001	Destabilizing	0.916	D	0.547	neutral	None	None	None	None	N
S/H	0.5544	ambiguous	0.5127	ambiguous	-1.541	Destabilizing	0.999	D	0.69	prob.neutral	None	None	None	None	N
S/I	0.3129	likely_benign	0.2872	benign	-0.229	Destabilizing	0.987	D	0.688	prob.neutral	None	None	None	None	N
S/K	0.8968	likely_pathogenic	0.8804	pathogenic	-0.702	Destabilizing	0.916	D	0.577	neutral	None	None	None	None	N
S/L	0.1844	likely_benign	0.1618	benign	-0.229	Destabilizing	0.987	D	0.645	neutral	None	None	None	None	N
S/M	0.2684	likely_benign	0.2714	benign	0.073	Stabilizing	0.999	D	0.689	prob.neutral	None	None	None	None	N
S/N	0.345	ambiguous	0.33	benign	-0.929	Destabilizing	0.845	D	0.579	neutral	None	None	None	None	N
S/P	0.9761	likely_pathogenic	0.9587	pathogenic	-0.375	Destabilizing	0.983	D	0.671	neutral	N	0.499819068	None	None	N
S/Q	0.686	likely_pathogenic	0.6737	pathogenic	-1.137	Destabilizing	0.987	D	0.646	neutral	None	None	None	None	N
S/R	0.8557	likely_pathogenic	0.8334	pathogenic	-0.579	Destabilizing	0.987	D	0.674	neutral	None	None	None	None	N
S/T	0.0841	likely_benign	0.0893	benign	-0.817	Destabilizing	0.892	D	0.549	neutral	N	0.423395127	None	None	N
S/V	0.2879	likely_benign	0.2724	benign	-0.375	Destabilizing	0.987	D	0.65	neutral	None	None	None	None	N
S/W	0.5682	likely_pathogenic	0.4741	ambiguous	-1.138	Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	N
S/Y	0.3643	ambiguous	0.2923	benign	-0.799	Destabilizing	0.994	D	0.713	prob.delet.	N	0.499565578	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.