TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14491	43696;43697;43698	chr2:178632535;178632534;178632533	chr2:179497262;179497261;179497260
N2AB	12850	38773;38774;38775	chr2:178632535;178632534;178632533	chr2:179497262;179497261;179497260
N2A	11923	35992;35993;35994	chr2:178632535;178632534;178632533	chr2:179497262;179497261;179497260
N2B	5426	16501;16502;16503	chr2:178632535;178632534;178632533	chr2:179497262;179497261;179497260
Novex-1	5551	16876;16877;16878	chr2:178632535;178632534;178632533	chr2:179497262;179497261;179497260
Novex-2	5618	17077;17078;17079	chr2:178632535;178632534;178632533	chr2:179497262;179497261;179497260
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-95
• Domain position: 84
• Structural Position: 178
• Q(SASA): 0.5315
• 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
I/V	rs765783194	None	0.132	N	0.126	0.064	0.530309751445	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	1.96567E-04	0	0	0	None	0	0	0	0	0
I/V	rs765783194	None	0.132	N	0.126	0.064	0.530309751445	gnomAD-4.0.0	1.97189E-05	None	None	None	None	N	None	0	1.96567E-04	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
I/A	0.6972	likely_pathogenic	0.6391	pathogenic	-1.677	Destabilizing	0.938	D	0.482	neutral	None	None	None	None	N
I/C	0.8716	likely_pathogenic	0.8468	pathogenic	-0.973	Destabilizing	0.999	D	0.543	neutral	None	None	None	None	N
I/D	0.8828	likely_pathogenic	0.895	pathogenic	-1.221	Destabilizing	0.997	D	0.599	neutral	None	None	None	None	N
I/E	0.7919	likely_pathogenic	0.7861	pathogenic	-1.188	Destabilizing	0.997	D	0.605	neutral	None	None	None	None	N
I/F	0.2366	likely_benign	0.1879	benign	-1.06	Destabilizing	0.076	N	0.218	neutral	N	0.470881175	None	None	N
I/G	0.8952	likely_pathogenic	0.8819	pathogenic	-2.023	Highly Destabilizing	0.997	D	0.596	neutral	None	None	None	None	N
I/H	0.5983	likely_pathogenic	0.5599	ambiguous	-1.157	Destabilizing	0.999	D	0.616	neutral	None	None	None	None	N
I/K	0.5762	likely_pathogenic	0.5794	pathogenic	-1.26	Destabilizing	0.997	D	0.603	neutral	None	None	None	None	N
I/L	0.1957	likely_benign	0.1659	benign	-0.785	Destabilizing	0.506	D	0.243	neutral	D	0.522124255	None	None	N
I/M	0.1735	likely_benign	0.1481	benign	-0.605	Destabilizing	0.988	D	0.483	neutral	N	0.496687616	None	None	N
I/N	0.4383	ambiguous	0.4354	ambiguous	-1.16	Destabilizing	0.996	D	0.609	neutral	D	0.523612939	None	None	N
I/P	0.9805	likely_pathogenic	0.9845	pathogenic	-1.052	Destabilizing	0.997	D	0.608	neutral	None	None	None	None	N
I/Q	0.6222	likely_pathogenic	0.5986	pathogenic	-1.297	Destabilizing	0.997	D	0.61	neutral	None	None	None	None	N
I/R	0.468	ambiguous	0.4505	ambiguous	-0.641	Destabilizing	0.997	D	0.611	neutral	None	None	None	None	N
I/S	0.5487	ambiguous	0.5106	ambiguous	-1.763	Destabilizing	0.988	D	0.519	neutral	N	0.518858746	None	None	N
I/T	0.4261	ambiguous	0.382	ambiguous	-1.615	Destabilizing	0.919	D	0.448	neutral	N	0.489964558	None	None	N
I/V	0.139	likely_benign	0.1199	benign	-1.052	Destabilizing	0.132	N	0.126	neutral	N	0.457585441	None	None	N
I/W	0.8405	likely_pathogenic	0.8272	pathogenic	-1.179	Destabilizing	0.999	D	0.631	neutral	None	None	None	None	N
I/Y	0.6043	likely_pathogenic	0.5876	pathogenic	-0.952	Destabilizing	0.964	D	0.486	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.