TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7132	21619;21620;21621	chr2:178723865;178723864;178723863	chr2:179588592;179588591;179588590
N2AB	6815	20668;20669;20670	chr2:178723865;178723864;178723863	chr2:179588592;179588591;179588590
N2A	5888	17887;17888;17889	chr2:178723865;178723864;178723863	chr2:179588592;179588591;179588590
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: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-55
• Domain position: 89
• Structural Position: 175
• Q(SASA): 0.4209
• 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
T/A	rs1450786655	None	None	N	0.099	0.184	0.207176502487	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	2.88018E-04	0	None	0	0	0	0	0
T/A	rs1450786655	None	None	N	0.099	0.184	0.207176502487	gnomAD-4.0.0	1.03036E-05	None	None	None	None	N	None	0	0	None	2.8866E-04	0	None	0	0	2.40963E-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
T/A	0.076	likely_benign	0.0752	benign	-0.717	Destabilizing	None	N	0.099	neutral	N	0.500545035	None	None	N
T/C	0.3778	ambiguous	0.41	ambiguous	-0.405	Destabilizing	0.824	D	0.411	neutral	None	None	None	None	N
T/D	0.2049	likely_benign	0.2028	benign	0.01	Stabilizing	0.38	N	0.405	neutral	None	None	None	None	N
T/E	0.1806	likely_benign	0.1762	benign	-0.015	Destabilizing	0.149	N	0.389	neutral	None	None	None	None	N
T/F	0.1448	likely_benign	0.1456	benign	-0.906	Destabilizing	None	N	0.225	neutral	None	None	None	None	N
T/G	0.2199	likely_benign	0.2251	benign	-0.942	Destabilizing	0.081	N	0.416	neutral	None	None	None	None	N
T/H	0.1562	likely_benign	0.1578	benign	-1.266	Destabilizing	0.935	D	0.431	neutral	None	None	None	None	N
T/I	0.1153	likely_benign	0.118	benign	-0.218	Destabilizing	0.062	N	0.365	neutral	N	0.5147245	None	None	N
T/K	0.1564	likely_benign	0.1507	benign	-0.591	Destabilizing	0.149	N	0.383	neutral	None	None	None	None	N
T/L	0.0803	likely_benign	0.0815	benign	-0.218	Destabilizing	0.001	N	0.169	neutral	None	None	None	None	N
T/M	0.0761	likely_benign	0.0779	benign	0.076	Stabilizing	0.38	N	0.427	neutral	None	None	None	None	N
T/N	0.0881	likely_benign	0.0893	benign	-0.442	Destabilizing	0.484	N	0.371	neutral	N	0.501717917	None	None	N
T/P	0.204	likely_benign	0.1968	benign	-0.353	Destabilizing	0.317	N	0.44	neutral	D	0.543896796	None	None	N
T/Q	0.1636	likely_benign	0.1598	benign	-0.649	Destabilizing	0.555	D	0.443	neutral	None	None	None	None	N
T/R	0.1125	likely_benign	0.1122	benign	-0.36	Destabilizing	0.38	N	0.44	neutral	None	None	None	None	N
T/S	0.089	likely_benign	0.0892	benign	-0.735	Destabilizing	0.027	N	0.279	neutral	N	0.519244885	None	None	N
T/V	0.1095	likely_benign	0.1115	benign	-0.353	Destabilizing	0.035	N	0.281	neutral	None	None	None	None	N
T/W	0.3527	ambiguous	0.3596	ambiguous	-0.828	Destabilizing	0.935	D	0.437	neutral	None	None	None	None	N
T/Y	0.1731	likely_benign	0.1732	benign	-0.59	Destabilizing	0.235	N	0.428	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.