TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29510	88753;88754;88755	chr2:178554931;178554930;178554929	chr2:179419658;179419657;179419656
N2AB	27869	83830;83831;83832	chr2:178554931;178554930;178554929	chr2:179419658;179419657;179419656
N2A	26942	81049;81050;81051	chr2:178554931;178554930;178554929	chr2:179419658;179419657;179419656
N2B	20445	61558;61559;61560	chr2:178554931;178554930;178554929	chr2:179419658;179419657;179419656
Novex-1	20570	61933;61934;61935	chr2:178554931;178554930;178554929	chr2:179419658;179419657;179419656
Novex-2	20637	62134;62135;62136	chr2:178554931;178554930;178554929	chr2:179419658;179419657;179419656
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Ig-146
• Domain position: 67
• Structural Position: 153
• Q(SASA): 0.2578
• 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
C/W	rs1396298450	-0.995	0.258	D	0.533	0.127	0.627302349016	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.65E-05	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
C/A	0.1372	likely_benign	0.1255	benign	-1.656	Destabilizing	None	N	0.159	neutral	None	None	None	None	N
C/D	0.1941	likely_benign	0.1692	benign	-0.503	Destabilizing	0.001	N	0.437	neutral	None	None	None	None	N
C/E	0.2923	likely_benign	0.247	benign	-0.416	Destabilizing	0.001	N	0.431	neutral	None	None	None	None	N
C/F	0.0846	likely_benign	0.0837	benign	-1.164	Destabilizing	0.013	N	0.415	neutral	N	0.48472688	None	None	N
C/G	0.0965	likely_benign	0.0893	benign	-1.945	Destabilizing	None	N	0.403	neutral	N	0.521378326	None	None	N
C/H	0.0975	likely_benign	0.0819	benign	-2.059	Highly Destabilizing	None	N	0.352	neutral	None	None	None	None	N
C/I	0.1308	likely_benign	0.1181	benign	-0.921	Destabilizing	0.001	N	0.345	neutral	None	None	None	None	N
C/K	0.1896	likely_benign	0.1472	benign	-0.91	Destabilizing	0.001	N	0.447	neutral	None	None	None	None	N
C/L	0.1483	likely_benign	0.1301	benign	-0.921	Destabilizing	None	N	0.277	neutral	None	None	None	None	N
C/M	0.247	likely_benign	0.2247	benign	-0.086	Destabilizing	0.041	N	0.509	neutral	None	None	None	None	N
C/N	0.0964	likely_benign	0.0839	benign	-0.852	Destabilizing	None	N	0.351	neutral	None	None	None	None	N
C/P	0.4821	ambiguous	0.427	ambiguous	-1.14	Destabilizing	0.004	N	0.421	neutral	None	None	None	None	N
C/Q	0.1614	likely_benign	0.1323	benign	-0.826	Destabilizing	0.004	N	0.417	neutral	None	None	None	None	N
C/R	0.0894	likely_benign	0.0714	benign	-0.783	Destabilizing	0.003	N	0.404	neutral	N	0.447515286	None	None	N
C/S	0.0793	likely_benign	0.075	benign	-1.366	Destabilizing	None	N	0.223	neutral	N	0.432449833	None	None	N
C/T	0.1123	likely_benign	0.102	benign	-1.105	Destabilizing	None	N	0.224	neutral	None	None	None	None	N
C/V	0.1445	likely_benign	0.1332	benign	-1.14	Destabilizing	None	N	0.213	neutral	None	None	None	None	N
C/W	0.1792	likely_benign	0.1742	benign	-1.165	Destabilizing	0.258	N	0.533	neutral	D	0.522071759	None	None	N
C/Y	0.083	likely_benign	0.0805	benign	-1.116	Destabilizing	0.007	N	0.389	neutral	N	0.492095569	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.