TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28049	84370;84371;84372	chr2:178561987;178561986;178561985	chr2:179426714;179426713;179426712
N2AB	26408	79447;79448;79449	chr2:178561987;178561986;178561985	chr2:179426714;179426713;179426712
N2A	25481	76666;76667;76668	chr2:178561987;178561986;178561985	chr2:179426714;179426713;179426712
N2B	18984	57175;57176;57177	chr2:178561987;178561986;178561985	chr2:179426714;179426713;179426712
Novex-1	19109	57550;57551;57552	chr2:178561987;178561986;178561985	chr2:179426714;179426713;179426712
Novex-2	19176	57751;57752;57753	chr2:178561987;178561986;178561985	chr2:179426714;179426713;179426712
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-142
• Domain position: 87
• Structural Position: 173
• Q(SASA): 0.3245
• 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	None	None	0.002	N	0.131	0.07	0.335414705075	gnomAD-4.0.0	1.59233E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85964E-06	0	0
T/I	rs762467183	0.374	0.81	N	0.481	0.246	0.623996689363	gnomAD-4.0.0	1.59233E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43336E-05	0
T/S	None	None	0.002	N	0.132	0.048	0.341226946553	gnomAD-4.0.0	3.18465E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71942E-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	0.0842	likely_benign	0.084	benign	-1.07	Destabilizing	0.002	N	0.131	neutral	N	0.495541306	None	None	N
T/C	0.3414	ambiguous	0.3694	ambiguous	-0.695	Destabilizing	0.992	D	0.461	neutral	None	None	None	None	N
T/D	0.2906	likely_benign	0.2894	benign	-0.387	Destabilizing	0.617	D	0.437	neutral	None	None	None	None	N
T/E	0.2481	likely_benign	0.2458	benign	-0.295	Destabilizing	0.617	D	0.466	neutral	None	None	None	None	N
T/F	0.2684	likely_benign	0.2831	benign	-0.922	Destabilizing	0.92	D	0.574	neutral	None	None	None	None	N
T/G	0.2241	likely_benign	0.2213	benign	-1.404	Destabilizing	0.002	N	0.268	neutral	None	None	None	None	N
T/H	0.164	likely_benign	0.1676	benign	-1.539	Destabilizing	0.977	D	0.546	neutral	None	None	None	None	N
T/I	0.1855	likely_benign	0.1878	benign	-0.24	Destabilizing	0.81	D	0.481	neutral	N	0.520746395	None	None	N
T/K	0.1375	likely_benign	0.1371	benign	-0.521	Destabilizing	0.447	N	0.454	neutral	None	None	None	None	N
T/L	0.1256	likely_benign	0.1262	benign	-0.24	Destabilizing	0.617	D	0.445	neutral	None	None	None	None	N
T/M	0.1128	likely_benign	0.1172	benign	-0.117	Destabilizing	0.972	D	0.465	neutral	None	None	None	None	N
T/N	0.0861	likely_benign	0.0823	benign	-0.749	Destabilizing	0.379	N	0.345	neutral	N	0.457753709	None	None	N
T/P	0.3002	likely_benign	0.3225	benign	-0.485	Destabilizing	0.896	D	0.471	neutral	D	0.531963466	None	None	N
T/Q	0.1664	likely_benign	0.1661	benign	-0.774	Destabilizing	0.85	D	0.49	neutral	None	None	None	None	N
T/R	0.1179	likely_benign	0.1246	benign	-0.476	Destabilizing	0.85	D	0.477	neutral	None	None	None	None	N
T/S	0.09	likely_benign	0.0872	benign	-1.107	Destabilizing	0.002	N	0.132	neutral	N	0.459156431	None	None	N
T/V	0.1487	likely_benign	0.1446	benign	-0.485	Destabilizing	0.447	N	0.348	neutral	None	None	None	None	N
T/W	0.6055	likely_pathogenic	0.6469	pathogenic	-0.859	Destabilizing	0.992	D	0.579	neutral	None	None	None	None	N
T/Y	0.2406	likely_benign	0.2557	benign	-0.58	Destabilizing	0.972	D	0.569	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.