TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27432	82519;82520;82521	chr2:178563838;178563837;178563836	chr2:179428565;179428564;179428563
N2AB	25791	77596;77597;77598	chr2:178563838;178563837;178563836	chr2:179428565;179428564;179428563
N2A	24864	74815;74816;74817	chr2:178563838;178563837;178563836	chr2:179428565;179428564;179428563
N2B	18367	55324;55325;55326	chr2:178563838;178563837;178563836	chr2:179428565;179428564;179428563
Novex-1	18492	55699;55700;55701	chr2:178563838;178563837;178563836	chr2:179428565;179428564;179428563
Novex-2	18559	55900;55901;55902	chr2:178563838;178563837;178563836	chr2:179428565;179428564;179428563
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-87
• Domain position: 64
• Structural Position: 94
• Q(SASA): 0.3002
• 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
T/N	None	None	0.988	N	0.6	0.364	0.449860987313	gnomAD-4.0.0	1.59136E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85845E-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
T/A	0.1708	likely_benign	0.1667	benign	-0.515	Destabilizing	0.958	D	0.432	neutral	D	0.523100762	None	None	N
T/C	0.5874	likely_pathogenic	0.5816	pathogenic	-0.472	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
T/D	0.6868	likely_pathogenic	0.7076	pathogenic	0.141	Stabilizing	0.991	D	0.674	neutral	None	None	None	None	N
T/E	0.6096	likely_pathogenic	0.6166	pathogenic	0.156	Stabilizing	0.938	D	0.547	neutral	None	None	None	None	N
T/F	0.4566	ambiguous	0.4605	ambiguous	-0.581	Destabilizing	0.998	D	0.812	deleterious	None	None	None	None	N
T/G	0.3153	likely_benign	0.3242	benign	-0.769	Destabilizing	0.991	D	0.683	prob.neutral	None	None	None	None	N
T/H	0.474	ambiguous	0.49	ambiguous	-0.917	Destabilizing	0.999	D	0.799	deleterious	None	None	None	None	N
T/I	0.3721	ambiguous	0.3476	ambiguous	0.063	Stabilizing	0.994	D	0.776	deleterious	D	0.525583706	None	None	N
T/K	0.4532	ambiguous	0.4611	ambiguous	-0.546	Destabilizing	0.938	D	0.634	neutral	None	None	None	None	N
T/L	0.159	likely_benign	0.1517	benign	0.063	Stabilizing	0.968	D	0.547	neutral	None	None	None	None	N
T/M	0.1332	likely_benign	0.1284	benign	-0.015	Destabilizing	0.999	D	0.773	deleterious	None	None	None	None	N
T/N	0.2032	likely_benign	0.2093	benign	-0.563	Destabilizing	0.988	D	0.6	neutral	N	0.517828228	None	None	N
T/P	0.1935	likely_benign	0.1672	benign	-0.097	Destabilizing	0.994	D	0.776	deleterious	D	0.522754045	None	None	N
T/Q	0.3872	ambiguous	0.3873	ambiguous	-0.616	Destabilizing	0.484	N	0.327	neutral	None	None	None	None	N
T/R	0.4234	ambiguous	0.4246	ambiguous	-0.361	Destabilizing	0.982	D	0.752	deleterious	None	None	None	None	N
T/S	0.168	likely_benign	0.1691	benign	-0.83	Destabilizing	0.958	D	0.399	neutral	N	0.479981916	None	None	N
T/V	0.2621	likely_benign	0.2416	benign	-0.097	Destabilizing	0.968	D	0.449	neutral	None	None	None	None	N
T/W	0.757	likely_pathogenic	0.7685	pathogenic	-0.601	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
T/Y	0.5382	ambiguous	0.5367	ambiguous	-0.324	Destabilizing	0.998	D	0.813	deleterious	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.