TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20965	63118;63119;63120	chr2:178588832;178588831;178588830	chr2:179453559;179453558;179453557
N2AB	19324	58195;58196;58197	chr2:178588832;178588831;178588830	chr2:179453559;179453558;179453557
N2A	18397	55414;55415;55416	chr2:178588832;178588831;178588830	chr2:179453559;179453558;179453557
N2B	11900	35923;35924;35925	chr2:178588832;178588831;178588830	chr2:179453559;179453558;179453557
Novex-1	12025	36298;36299;36300	chr2:178588832;178588831;178588830	chr2:179453559;179453558;179453557
Novex-2	12092	36499;36500;36501	chr2:178588832;178588831;178588830	chr2:179453559;179453558;179453557
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Fn3-40
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.1863
• 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
G/D	None	None	1.0	N	0.749	0.351	0.32714864917	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
G/S	rs753424257	None	1.0	N	0.725	0.395	0.32714864917	gnomAD-4.0.0	7.528E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99585E-06	0	1.657E-05

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
G/A	0.3278	likely_benign	0.2914	benign	-0.824	Destabilizing	1.0	D	0.62	neutral	N	0.489762528	None	None	N
G/C	0.5134	ambiguous	0.4619	ambiguous	-1.095	Destabilizing	1.0	D	0.765	deleterious	N	0.509894699	None	None	N
G/D	0.535	ambiguous	0.49	ambiguous	-1.685	Destabilizing	1.0	D	0.749	deleterious	N	0.468238005	None	None	N
G/E	0.6815	likely_pathogenic	0.6086	pathogenic	-1.726	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
G/F	0.8971	likely_pathogenic	0.8863	pathogenic	-1.092	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
G/H	0.7897	likely_pathogenic	0.7579	pathogenic	-1.422	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
G/I	0.8944	likely_pathogenic	0.8419	pathogenic	-0.406	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
G/K	0.8472	likely_pathogenic	0.7902	pathogenic	-1.297	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
G/L	0.8295	likely_pathogenic	0.7853	pathogenic	-0.406	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
G/M	0.877	likely_pathogenic	0.8399	pathogenic	-0.41	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
G/N	0.6976	likely_pathogenic	0.6498	pathogenic	-1.044	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
G/P	0.9861	likely_pathogenic	0.9839	pathogenic	-0.505	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
G/Q	0.709	likely_pathogenic	0.646	pathogenic	-1.244	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
G/R	0.7562	likely_pathogenic	0.7005	pathogenic	-1.007	Destabilizing	1.0	D	0.795	deleterious	N	0.497524436	None	None	N
G/S	0.1798	likely_benign	0.1684	benign	-1.267	Destabilizing	1.0	D	0.725	prob.delet.	N	0.476045457	None	None	N
G/T	0.5517	ambiguous	0.5021	ambiguous	-1.24	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
G/V	0.8074	likely_pathogenic	0.7454	pathogenic	-0.505	Destabilizing	1.0	D	0.78	deleterious	N	0.50938772	None	None	N
G/W	0.8172	likely_pathogenic	0.8066	pathogenic	-1.462	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
G/Y	0.8205	likely_pathogenic	0.7845	pathogenic	-1.055	Destabilizing	1.0	D	0.77	deleterious	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.