TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6155	18688;18689;18690	chr2:178729790;178729789;178729788	chr2:179594517;179594516;179594515
N2AB	5838	17737;17738;17739	chr2:178729790;178729789;178729788	chr2:179594517;179594516;179594515
N2A	4911	14956;14957;14958	chr2:178729790;178729789;178729788	chr2:179594517;179594516;179594515
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: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-45
• Domain position: 51
• Structural Position: 125
• Q(SASA): 0.3391
• 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/A	rs768149481	-0.247	0.248	D	0.131	0.138	0.272639205421	gnomAD-2.1.1	1.07E-05	None	None	None	None	N	None	0	0	None	0	1.53941E-04	None	0	None	0	0	0
S/A	rs768149481	-0.247	0.248	D	0.131	0.138	0.272639205421	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.93125E-04	None	0	0	0	0	0
S/A	rs768149481	-0.247	0.248	D	0.131	0.138	0.272639205421	gnomAD-4.0.0	1.85913E-06	None	None	None	None	N	None	0	0	None	0	6.68777E-05	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
S/A	0.0864	likely_benign	0.0911	benign	-0.484	Destabilizing	0.248	N	0.131	neutral	D	0.526728218	None	None	N
S/C	0.1594	likely_benign	0.1728	benign	-0.323	Destabilizing	1.0	D	0.497	neutral	D	0.524867489	None	None	N
S/D	0.3001	likely_benign	0.29	benign	0.44	Stabilizing	0.985	D	0.404	neutral	None	None	None	None	N
S/E	0.3906	ambiguous	0.3876	ambiguous	0.404	Stabilizing	0.985	D	0.401	neutral	None	None	None	None	N
S/F	0.1425	likely_benign	0.1531	benign	-0.873	Destabilizing	0.989	D	0.584	neutral	N	0.494330518	None	None	N
S/G	0.1263	likely_benign	0.127	benign	-0.675	Destabilizing	0.97	D	0.41	neutral	None	None	None	None	N
S/H	0.2449	likely_benign	0.246	benign	-1.095	Destabilizing	1.0	D	0.499	neutral	None	None	None	None	N
S/I	0.1523	likely_benign	0.1542	benign	-0.098	Destabilizing	0.942	D	0.506	neutral	None	None	None	None	N
S/K	0.4889	ambiguous	0.497	ambiguous	-0.372	Destabilizing	0.97	D	0.401	neutral	None	None	None	None	N
S/L	0.1006	likely_benign	0.1045	benign	-0.098	Destabilizing	0.092	N	0.329	neutral	None	None	None	None	N
S/M	0.2202	likely_benign	0.2292	benign	0.004	Stabilizing	0.991	D	0.508	neutral	None	None	None	None	N
S/N	0.1424	likely_benign	0.1373	benign	-0.252	Destabilizing	0.985	D	0.439	neutral	None	None	None	None	N
S/P	0.5614	ambiguous	0.562	ambiguous	-0.193	Destabilizing	0.994	D	0.468	neutral	D	0.52436051	None	None	N
S/Q	0.3848	ambiguous	0.3863	ambiguous	-0.374	Destabilizing	0.999	D	0.457	neutral	None	None	None	None	N
S/R	0.3653	ambiguous	0.37	ambiguous	-0.279	Destabilizing	0.996	D	0.472	neutral	None	None	None	None	N
S/T	0.0788	likely_benign	0.0828	benign	-0.335	Destabilizing	0.248	N	0.207	neutral	N	0.484302805	None	None	N
S/V	0.1602	likely_benign	0.1666	benign	-0.193	Destabilizing	0.942	D	0.504	neutral	None	None	None	None	N
S/W	0.2563	likely_benign	0.2719	benign	-0.876	Destabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	N
S/Y	0.1287	likely_benign	0.1353	benign	-0.581	Destabilizing	0.998	D	0.588	neutral	N	0.498115953	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.