TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6903	20932;20933;20934	chr2:178725497;178725496;178725495	chr2:179590224;179590223;179590222
N2AB	6586	19981;19982;19983	chr2:178725497;178725496;178725495	chr2:179590224;179590223;179590222
N2A	5659	17200;17201;17202	chr2:178725497;178725496;178725495	chr2:179590224;179590223;179590222
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: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-53
• Domain position: 50
• Structural Position: 123
• Q(SASA): 0.2866
• 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
I/V	rs571675433	-1.205	0.911	N	0.353	0.219	0.63713380425	gnomAD-2.1.1	3.62E-05	None	None	None	None	I	None	0	0	None	0	0	None	2.94426E-04	None	0	0	0
I/V	rs571675433	-1.205	0.911	N	0.353	0.219	0.63713380425	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	6.20091E-04	0
I/V	rs571675433	-1.205	0.911	N	0.353	0.219	0.63713380425	1000 genomes	3.99361E-04	None	None	None	None	I	None	0	0	None	None	0	0	None	None	None	2E-03	None
I/V	rs571675433	-1.205	0.911	N	0.353	0.219	0.63713380425	gnomAD-4.0.0	1.73539E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	1.65125E-04	0	2.96579E-04	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	0.6715	likely_pathogenic	0.6769	pathogenic	-2.037	Highly Destabilizing	0.985	D	0.49	neutral	None	None	None	None	I
I/C	0.7874	likely_pathogenic	0.7891	pathogenic	-1.208	Destabilizing	1.0	D	0.587	neutral	None	None	None	None	I
I/D	0.9274	likely_pathogenic	0.932	pathogenic	-1.668	Destabilizing	0.998	D	0.677	prob.neutral	None	None	None	None	I
I/E	0.8048	likely_pathogenic	0.8217	pathogenic	-1.594	Destabilizing	0.996	D	0.653	neutral	None	None	None	None	I
I/F	0.1798	likely_benign	0.1759	benign	-1.355	Destabilizing	0.997	D	0.476	neutral	N	0.505295203	None	None	I
I/G	0.8634	likely_pathogenic	0.8724	pathogenic	-2.448	Highly Destabilizing	0.998	D	0.65	neutral	None	None	None	None	I
I/H	0.7383	likely_pathogenic	0.7332	pathogenic	-1.723	Destabilizing	0.323	N	0.477	neutral	None	None	None	None	I
I/K	0.5812	likely_pathogenic	0.5762	pathogenic	-1.478	Destabilizing	0.998	D	0.659	neutral	None	None	None	None	I
I/L	0.1351	likely_benign	0.1337	benign	-0.934	Destabilizing	0.817	D	0.318	neutral	N	0.511798838	None	None	I
I/M	0.0809	likely_benign	0.0829	benign	-0.697	Destabilizing	0.817	D	0.347	neutral	D	0.526672289	None	None	I
I/N	0.5656	likely_pathogenic	0.5758	pathogenic	-1.382	Destabilizing	0.994	D	0.677	prob.neutral	D	0.525173885	None	None	I
I/P	0.9304	likely_pathogenic	0.9287	pathogenic	-1.274	Destabilizing	0.999	D	0.704	prob.neutral	None	None	None	None	I
I/Q	0.6489	likely_pathogenic	0.6441	pathogenic	-1.467	Destabilizing	0.998	D	0.704	prob.neutral	None	None	None	None	I
I/R	0.5412	ambiguous	0.5226	ambiguous	-0.957	Destabilizing	0.996	D	0.687	prob.neutral	None	None	None	None	I
I/S	0.6373	likely_pathogenic	0.6449	pathogenic	-2.034	Highly Destabilizing	0.99	D	0.597	neutral	D	0.524413416	None	None	I
I/T	0.5961	likely_pathogenic	0.611	pathogenic	-1.83	Destabilizing	0.99	D	0.537	neutral	N	0.489672937	None	None	I
I/V	0.1148	likely_benign	0.1137	benign	-1.274	Destabilizing	0.911	D	0.353	neutral	N	0.516220436	None	None	I
I/W	0.7848	likely_pathogenic	0.785	pathogenic	-1.532	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
I/Y	0.5273	ambiguous	0.5297	ambiguous	-1.292	Destabilizing	0.996	D	0.562	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.