TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8617	26074;26075;26076	chr2:178715565;178715564;178715563	chr2:179580292;179580291;179580290
N2AB	8300	25123;25124;25125	chr2:178715565;178715564;178715563	chr2:179580292;179580291;179580290
N2A	7373	22342;22343;22344	chr2:178715565;178715564;178715563	chr2:179580292;179580291;179580290
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-71
• Domain position: 69
• Structural Position: 151
• Q(SASA): 0.3049
• 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/I	None	None	0.84	D	0.572	0.359	0.732098058403	gnomAD-4.0.0	1.5916E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85914E-06	0	0
S/N	rs1361559046	-0.497	0.001	N	0.198	0.173	0.213573922156	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
S/N	rs1361559046	-0.497	0.001	N	0.198	0.173	0.213573922156	gnomAD-4.0.0	6.36641E-06	None	None	None	None	N	None	0	0	None	0	2.77316E-05	None	0	0	8.57741E-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	0.1162	likely_benign	0.1256	benign	-0.728	Destabilizing	0.016	N	0.44	neutral	None	None	None	None	N
S/C	0.2825	likely_benign	0.2719	benign	-0.501	Destabilizing	0.985	D	0.534	neutral	D	0.534212786	None	None	N
S/D	0.7487	likely_pathogenic	0.6909	pathogenic	0.012	Stabilizing	0.001	N	0.137	neutral	None	None	None	None	N
S/E	0.8177	likely_pathogenic	0.7744	pathogenic	-0.001	Destabilizing	0.234	N	0.494	neutral	None	None	None	None	N
S/F	0.577	likely_pathogenic	0.561	ambiguous	-0.957	Destabilizing	0.966	D	0.603	neutral	None	None	None	None	N
S/G	0.1488	likely_benign	0.1293	benign	-0.958	Destabilizing	0.379	N	0.479	neutral	D	0.538140077	None	None	N
S/H	0.7495	likely_pathogenic	0.7157	pathogenic	-1.38	Destabilizing	0.966	D	0.548	neutral	None	None	None	None	N
S/I	0.4836	ambiguous	0.4452	ambiguous	-0.226	Destabilizing	0.84	D	0.572	neutral	D	0.525312016	None	None	N
S/K	0.9279	likely_pathogenic	0.8932	pathogenic	-0.594	Destabilizing	0.798	D	0.487	neutral	None	None	None	None	N
S/L	0.2406	likely_benign	0.2293	benign	-0.226	Destabilizing	0.664	D	0.543	neutral	None	None	None	None	N
S/M	0.3814	ambiguous	0.3686	ambiguous	0.044	Stabilizing	0.991	D	0.535	neutral	None	None	None	None	N
S/N	0.3704	ambiguous	0.3239	benign	-0.532	Destabilizing	0.001	N	0.198	neutral	N	0.512941752	None	None	N
S/P	0.9337	likely_pathogenic	0.8991	pathogenic	-0.36	Destabilizing	0.883	D	0.525	neutral	None	None	None	None	N
S/Q	0.8161	likely_pathogenic	0.781	pathogenic	-0.7	Destabilizing	0.966	D	0.503	neutral	None	None	None	None	N
S/R	0.8612	likely_pathogenic	0.818	pathogenic	-0.472	Destabilizing	0.913	D	0.531	neutral	N	0.505206298	None	None	N
S/T	0.1223	likely_benign	0.1069	benign	-0.613	Destabilizing	None	N	0.161	neutral	N	0.50529694	None	None	N
S/V	0.4841	ambiguous	0.4523	ambiguous	-0.36	Destabilizing	0.425	N	0.537	neutral	None	None	None	None	N
S/W	0.7705	likely_pathogenic	0.7352	pathogenic	-0.901	Destabilizing	0.997	D	0.666	neutral	None	None	None	None	N
S/Y	0.556	ambiguous	0.5406	ambiguous	-0.643	Destabilizing	0.988	D	0.593	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.