TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31300	94123;94124;94125	chr2:178547728;178547727;178547726	chr2:179412455;179412454;179412453
N2AB	29659	89200;89201;89202	chr2:178547728;178547727;178547726	chr2:179412455;179412454;179412453
N2A	28732	86419;86420;86421	chr2:178547728;178547727;178547726	chr2:179412455;179412454;179412453
N2B	22235	66928;66929;66930	chr2:178547728;178547727;178547726	chr2:179412455;179412454;179412453
Novex-1	22360	67303;67304;67305	chr2:178547728;178547727;178547726	chr2:179412455;179412454;179412453
Novex-2	22427	67504;67505;67506	chr2:178547728;178547727;178547726	chr2:179412455;179412454;179412453
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: Ig-151
• Domain position: 83
• Structural Position: 171
• Q(SASA): 0.3097
• 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/G	None	None	0.01	N	0.267	0.303	0.303123707472	gnomAD-4.0.0	1.59106E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8578E-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	0.0669	likely_benign	0.0635	benign	-0.688	Destabilizing	None	N	0.107	neutral	None	None	None	None	N
S/C	0.1086	likely_benign	0.1115	benign	-0.396	Destabilizing	0.295	N	0.535	neutral	N	0.504485509	None	None	N
S/D	0.3174	likely_benign	0.2733	benign	0.418	Stabilizing	0.031	N	0.347	neutral	None	None	None	None	N
S/E	0.3487	ambiguous	0.2985	benign	0.428	Stabilizing	0.031	N	0.354	neutral	None	None	None	None	N
S/F	0.1597	likely_benign	0.1689	benign	-0.812	Destabilizing	0.072	N	0.659	neutral	None	None	None	None	N
S/G	0.1115	likely_benign	0.1007	benign	-0.94	Destabilizing	0.01	N	0.267	neutral	N	0.503218061	None	None	N
S/H	0.2708	likely_benign	0.2478	benign	-1.278	Destabilizing	0.628	D	0.545	neutral	None	None	None	None	N
S/I	0.1089	likely_benign	0.1226	benign	-0.12	Destabilizing	None	N	0.283	neutral	D	0.530963388	None	None	N
S/K	0.5346	ambiguous	0.4628	ambiguous	-0.392	Destabilizing	0.031	N	0.351	neutral	None	None	None	None	N
S/L	0.0779	likely_benign	0.0801	benign	-0.12	Destabilizing	0.007	N	0.358	neutral	None	None	None	None	N
S/M	0.1236	likely_benign	0.1179	benign	-0.042	Destabilizing	0.356	N	0.547	neutral	None	None	None	None	N
S/N	0.1207	likely_benign	0.1085	benign	-0.322	Destabilizing	0.024	N	0.36	neutral	N	0.500640481	None	None	N
S/P	0.1284	likely_benign	0.0971	benign	-0.275	Destabilizing	0.136	N	0.513	neutral	None	None	None	None	N
S/Q	0.3957	ambiguous	0.3375	benign	-0.402	Destabilizing	0.136	N	0.467	neutral	None	None	None	None	N
S/R	0.459	ambiguous	0.4017	ambiguous	-0.38	Destabilizing	0.13	N	0.547	neutral	N	0.514839143	None	None	N
S/T	0.0577	likely_benign	0.0597	benign	-0.415	Destabilizing	None	N	0.111	neutral	N	0.442149538	None	None	N
S/V	0.1201	likely_benign	0.1196	benign	-0.275	Destabilizing	0.003	N	0.361	neutral	None	None	None	None	N
S/W	0.2691	likely_benign	0.2873	benign	-0.773	Destabilizing	0.864	D	0.611	neutral	None	None	None	None	N
S/Y	0.1673	likely_benign	0.1692	benign	-0.497	Destabilizing	0.356	N	0.661	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.