TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5514	16765;16766;16767	chr2:178732521;178732520;178732519	chr2:179597248;179597247;179597246
N2AB	5197	15814;15815;15816	chr2:178732521;178732520;178732519	chr2:179597248;179597247;179597246
N2A	4270	13033;13034;13035	chr2:178732521;178732520;178732519	chr2:179597248;179597247;179597246
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: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-38
• Domain position: 65
• Structural Position: 146
• Q(SASA): 0.7191
• Predicted PPI site: I

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/I	None	None	0.004	N	0.175	0.088	0.163833314356	gnomAD-4.0.0	1.59152E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85847E-06	0	0
T/N	rs2080735339	None	0.896	N	0.247	0.178	0.197625483188	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
T/N	rs2080735339	None	0.896	N	0.247	0.178	0.197625483188	gnomAD-4.0.0	6.57255E-06	None	None	None	None	I	None	2.41336E-05	0	None	0	0	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
T/A	0.0672	likely_benign	0.0651	benign	-0.435	Destabilizing	0.334	N	0.267	neutral	N	0.4424311	None	None	I
T/C	0.3753	ambiguous	0.4088	ambiguous	-0.264	Destabilizing	0.992	D	0.271	neutral	None	None	None	None	I
T/D	0.2515	likely_benign	0.2802	benign	0.348	Stabilizing	0.766	D	0.321	neutral	None	None	None	None	I
T/E	0.2029	likely_benign	0.2192	benign	0.279	Stabilizing	0.617	D	0.341	neutral	None	None	None	None	I
T/F	0.2001	likely_benign	0.2247	benign	-0.893	Destabilizing	0.85	D	0.323	neutral	None	None	None	None	I
T/G	0.1766	likely_benign	0.1934	benign	-0.576	Destabilizing	0.617	D	0.339	neutral	None	None	None	None	I
T/H	0.1831	likely_benign	0.2033	benign	-0.87	Destabilizing	0.992	D	0.291	neutral	None	None	None	None	I
T/I	0.1097	likely_benign	0.1173	benign	-0.182	Destabilizing	0.004	N	0.175	neutral	N	0.477063749	None	None	I
T/K	0.1393	likely_benign	0.1425	benign	-0.299	Destabilizing	0.617	D	0.335	neutral	None	None	None	None	I
T/L	0.0796	likely_benign	0.0836	benign	-0.182	Destabilizing	0.103	N	0.309	neutral	None	None	None	None	I
T/M	0.081	likely_benign	0.0841	benign	0.041	Stabilizing	0.85	D	0.267	neutral	None	None	None	None	I
T/N	0.0828	likely_benign	0.0878	benign	-0.087	Destabilizing	0.896	D	0.247	neutral	N	0.497959096	None	None	I
T/P	0.0575	likely_benign	0.0577	benign	-0.237	Destabilizing	0.001	N	0.128	neutral	N	0.380131848	None	None	I
T/Q	0.1592	likely_benign	0.1707	benign	-0.318	Destabilizing	0.92	D	0.282	neutral	None	None	None	None	I
T/R	0.1276	likely_benign	0.1301	benign	-0.05	Destabilizing	0.92	D	0.295	neutral	None	None	None	None	I
T/S	0.0896	likely_benign	0.0946	benign	-0.36	Destabilizing	0.549	D	0.251	neutral	N	0.43450505	None	None	I
T/V	0.103	likely_benign	0.1059	benign	-0.237	Destabilizing	0.021	N	0.115	neutral	None	None	None	None	I
T/W	0.511	ambiguous	0.5666	pathogenic	-0.862	Destabilizing	0.992	D	0.351	neutral	None	None	None	None	I
T/Y	0.1988	likely_benign	0.2278	benign	-0.583	Destabilizing	0.92	D	0.303	neutral	None	None	None	None	I

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.