TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30735	92428;92429;92430	chr2:178549423;178549422;178549421	chr2:179414150;179414149;179414148
N2AB	29094	87505;87506;87507	chr2:178549423;178549422;178549421	chr2:179414150;179414149;179414148
N2A	28167	84724;84725;84726	chr2:178549423;178549422;178549421	chr2:179414150;179414149;179414148
N2B	21670	65233;65234;65235	chr2:178549423;178549422;178549421	chr2:179414150;179414149;179414148
Novex-1	21795	65608;65609;65610	chr2:178549423;178549422;178549421	chr2:179414150;179414149;179414148
Novex-2	21862	65809;65810;65811	chr2:178549423;178549422;178549421	chr2:179414150;179414149;179414148
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Fn3-112
• Domain position: 17
• Structural Position: 19
• Q(SASA): 0.1265
• 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/N	rs1225964281	None	0.994	N	0.497	0.374	0.318828661733	gnomAD-4.0.0	1.36972E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80069E-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	0.1132	likely_benign	0.1456	benign	-0.459	Destabilizing	0.98	D	0.436	neutral	None	None	None	None	N
S/C	0.1101	likely_benign	0.1343	benign	-0.928	Destabilizing	1.0	D	0.749	deleterious	N	0.514540551	None	None	N
S/D	0.7759	likely_pathogenic	0.8331	pathogenic	-1.82	Destabilizing	0.996	D	0.481	neutral	None	None	None	None	N
S/E	0.815	likely_pathogenic	0.8532	pathogenic	-1.776	Destabilizing	0.996	D	0.489	neutral	None	None	None	None	N
S/F	0.2784	likely_benign	0.3721	ambiguous	-0.938	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
S/G	0.1644	likely_benign	0.1858	benign	-0.67	Destabilizing	0.994	D	0.443	neutral	N	0.510310589	None	None	N
S/H	0.4923	ambiguous	0.5501	ambiguous	-1.208	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
S/I	0.4358	ambiguous	0.5324	ambiguous	-0.001	Destabilizing	0.997	D	0.801	deleterious	D	0.545393464	None	None	N
S/K	0.9424	likely_pathogenic	0.964	pathogenic	-0.561	Destabilizing	0.996	D	0.481	neutral	None	None	None	None	N
S/L	0.2058	likely_benign	0.2787	benign	-0.001	Destabilizing	0.992	D	0.664	neutral	None	None	None	None	N
S/M	0.2587	likely_benign	0.3311	benign	0.165	Stabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
S/N	0.2951	likely_benign	0.3312	benign	-1.023	Destabilizing	0.994	D	0.497	neutral	N	0.505777912	None	None	N
S/P	0.9914	likely_pathogenic	0.9945	pathogenic	-0.123	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
S/Q	0.728	likely_pathogenic	0.7736	pathogenic	-1.246	Destabilizing	1.0	D	0.63	neutral	None	None	None	None	N
S/R	0.9074	likely_pathogenic	0.9391	pathogenic	-0.426	Destabilizing	0.998	D	0.765	deleterious	D	0.527996771	None	None	N
S/T	0.1068	likely_benign	0.1216	benign	-0.748	Destabilizing	0.543	D	0.369	neutral	D	0.526874572	None	None	N
S/V	0.3683	ambiguous	0.4687	ambiguous	-0.123	Destabilizing	0.998	D	0.731	prob.delet.	None	None	None	None	N
S/W	0.5751	likely_pathogenic	0.6629	pathogenic	-1.091	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
S/Y	0.2784	likely_benign	0.35	ambiguous	-0.65	Destabilizing	1.0	D	0.823	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.