TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17406	52441;52442;52443	chr2:178608795;178608794;178608793	chr2:179473522;179473521;179473520
N2AB	15765	47518;47519;47520	chr2:178608795;178608794;178608793	chr2:179473522;179473521;179473520
N2A	14838	44737;44738;44739	chr2:178608795;178608794;178608793	chr2:179473522;179473521;179473520
N2B	8341	25246;25247;25248	chr2:178608795;178608794;178608793	chr2:179473522;179473521;179473520
Novex-1	8466	25621;25622;25623	chr2:178608795;178608794;178608793	chr2:179473522;179473521;179473520
Novex-2	8533	25822;25823;25824	chr2:178608795;178608794;178608793	chr2:179473522;179473521;179473520
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Fn3-14
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.0762
• 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/S	rs1370237214	None	0.999	N	0.858	0.582	0.816087557028	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	2.75482E-04	None	0	0	0	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	0.9378	likely_pathogenic	0.947	pathogenic	-2.901	Highly Destabilizing	0.997	D	0.71	prob.delet.	None	None	None	None	N
L/C	0.9429	likely_pathogenic	0.9501	pathogenic	-1.886	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
L/D	0.9998	likely_pathogenic	0.9998	pathogenic	-3.533	Highly Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
L/E	0.9979	likely_pathogenic	0.998	pathogenic	-3.195	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
L/F	0.8157	likely_pathogenic	0.812	pathogenic	-1.731	Destabilizing	0.999	D	0.775	deleterious	N	0.508154088	None	None	N
L/G	0.9962	likely_pathogenic	0.9966	pathogenic	-3.517	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
L/H	0.9969	likely_pathogenic	0.9972	pathogenic	-3.19	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
L/I	0.1369	likely_benign	0.1261	benign	-1.024	Destabilizing	0.994	D	0.628	neutral	None	None	None	None	N
L/K	0.997	likely_pathogenic	0.997	pathogenic	-2.192	Highly Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
L/M	0.358	ambiguous	0.3362	benign	-1.178	Destabilizing	0.999	D	0.733	prob.delet.	N	0.473667098	None	None	N
L/N	0.9989	likely_pathogenic	0.999	pathogenic	-2.979	Highly Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
L/P	0.9979	likely_pathogenic	0.9981	pathogenic	-1.644	Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
L/Q	0.9945	likely_pathogenic	0.9948	pathogenic	-2.577	Highly Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
L/R	0.9937	likely_pathogenic	0.9939	pathogenic	-2.325	Highly Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
L/S	0.9967	likely_pathogenic	0.997	pathogenic	-3.484	Highly Destabilizing	0.999	D	0.858	deleterious	N	0.508407577	None	None	N
L/T	0.964	likely_pathogenic	0.9666	pathogenic	-2.976	Highly Destabilizing	0.999	D	0.796	deleterious	None	None	None	None	N
L/V	0.1214	likely_benign	0.1247	benign	-1.644	Destabilizing	0.767	D	0.403	neutral	N	0.375016816	None	None	N
L/W	0.9887	likely_pathogenic	0.9878	pathogenic	-2.061	Highly Destabilizing	1.0	D	0.805	deleterious	N	0.508407577	None	None	N
L/Y	0.9903	likely_pathogenic	0.9902	pathogenic	-1.923	Destabilizing	1.0	D	0.82	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.