TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6284	19075;19076;19077	chr2:178729306;178729305;178729304	chr2:179594033;179594032;179594031
N2AB	5967	18124;18125;18126	chr2:178729306;178729305;178729304	chr2:179594033;179594032;179594031
N2A	5040	15343;15344;15345	chr2:178729306;178729305;178729304	chr2:179594033;179594032;179594031
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: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-46
• Domain position: 86
• Structural Position: 172
• Q(SASA): 0.1115
• 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	None	N	0.17	0.194	0.0138822411134	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
T/I	None	None	0.317	N	0.789	0.257	0.303781844768	gnomAD-4.0.0	1.59887E-06	None	None	None	None	N	None	0	0	None	0	2.77731E-05	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	0.0595	likely_benign	0.0596	benign	-1.113	Destabilizing	None	N	0.17	neutral	N	0.343827984	None	None	N
T/C	0.3368	likely_benign	0.3516	ambiguous	-0.777	Destabilizing	0.824	D	0.756	deleterious	None	None	None	None	N
T/D	0.6427	likely_pathogenic	0.7034	pathogenic	-0.885	Destabilizing	0.149	N	0.769	deleterious	None	None	None	None	N
T/E	0.5876	likely_pathogenic	0.6303	pathogenic	-0.764	Destabilizing	0.149	N	0.734	prob.delet.	None	None	None	None	N
T/F	0.4747	ambiguous	0.5226	ambiguous	-0.887	Destabilizing	0.555	D	0.783	deleterious	None	None	None	None	N
T/G	0.1839	likely_benign	0.2099	benign	-1.489	Destabilizing	0.035	N	0.637	neutral	None	None	None	None	N
T/H	0.5253	ambiguous	0.5709	pathogenic	-1.698	Destabilizing	0.935	D	0.745	deleterious	None	None	None	None	N
T/I	0.3199	likely_benign	0.3249	benign	-0.158	Destabilizing	0.317	N	0.789	deleterious	N	0.466370405	None	None	N
T/K	0.5408	ambiguous	0.6017	pathogenic	-0.741	Destabilizing	0.149	N	0.744	deleterious	None	None	None	None	N
T/L	0.1891	likely_benign	0.2055	benign	-0.158	Destabilizing	0.081	N	0.68	prob.neutral	None	None	None	None	N
T/M	0.1396	likely_benign	0.1393	benign	0.001	Stabilizing	0.555	D	0.76	deleterious	None	None	None	None	N
T/N	0.2701	likely_benign	0.2967	benign	-1.106	Destabilizing	0.117	N	0.7	prob.neutral	N	0.515396503	None	None	N
T/P	0.6076	likely_pathogenic	0.685	pathogenic	-0.443	Destabilizing	0.317	N	0.797	deleterious	D	0.526613574	None	None	N
T/Q	0.4506	ambiguous	0.4883	ambiguous	-1.046	Destabilizing	0.555	D	0.788	deleterious	None	None	None	None	N
T/R	0.4283	ambiguous	0.4752	ambiguous	-0.773	Destabilizing	0.38	N	0.797	deleterious	None	None	None	None	N
T/S	0.1046	likely_benign	0.1105	benign	-1.39	Destabilizing	0.005	N	0.214	neutral	N	0.415309654	None	None	N
T/V	0.1826	likely_benign	0.1871	benign	-0.443	Destabilizing	0.081	N	0.59	neutral	None	None	None	None	N
T/W	0.8373	likely_pathogenic	0.8607	pathogenic	-0.901	Destabilizing	0.935	D	0.751	deleterious	None	None	None	None	N
T/Y	0.5586	ambiguous	0.6087	pathogenic	-0.603	Destabilizing	0.555	D	0.756	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.