TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24085	72478;72479;72480	chr2:178573879;178573878;178573877	chr2:179438606;179438605;179438604
N2AB	22444	67555;67556;67557	chr2:178573879;178573878;178573877	chr2:179438606;179438605;179438604
N2A	21517	64774;64775;64776	chr2:178573879;178573878;178573877	chr2:179438606;179438605;179438604
N2B	15020	45283;45284;45285	chr2:178573879;178573878;178573877	chr2:179438606;179438605;179438604
Novex-1	15145	45658;45659;45660	chr2:178573879;178573878;178573877	chr2:179438606;179438605;179438604
Novex-2	15212	45859;45860;45861	chr2:178573879;178573878;178573877	chr2:179438606;179438605;179438604
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-131
• Domain position: 57
• Structural Position: 136
• Q(SASA): 0.114
• 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/N	rs1317961442	-0.932	0.982	N	0.725	0.335	0.248417906384	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
T/N	rs1317961442	-0.932	0.982	N	0.725	0.335	0.248417906384	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/N	rs1317961442	-0.932	0.982	N	0.725	0.335	0.248417906384	gnomAD-4.0.0	6.57289E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.4705E-05	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	0.1026	likely_benign	0.1057	benign	-1.212	Destabilizing	0.046	N	0.485	neutral	N	0.46540396	None	None	N
T/C	0.4706	ambiguous	0.434	ambiguous	-1.092	Destabilizing	0.999	D	0.734	prob.delet.	None	None	None	None	N
T/D	0.9594	likely_pathogenic	0.9532	pathogenic	-1.89	Destabilizing	0.986	D	0.743	deleterious	None	None	None	None	N
T/E	0.9537	likely_pathogenic	0.9486	pathogenic	-1.648	Destabilizing	0.986	D	0.743	deleterious	None	None	None	None	N
T/F	0.8807	likely_pathogenic	0.8553	pathogenic	-0.878	Destabilizing	0.993	D	0.763	deleterious	None	None	None	None	N
T/G	0.5094	ambiguous	0.4945	ambiguous	-1.67	Destabilizing	0.91	D	0.723	prob.delet.	None	None	None	None	N
T/H	0.8838	likely_pathogenic	0.8684	pathogenic	-1.796	Destabilizing	0.999	D	0.752	deleterious	None	None	None	None	N
T/I	0.7495	likely_pathogenic	0.7163	pathogenic	0.01	Stabilizing	0.982	D	0.736	prob.delet.	N	0.472960222	None	None	N
T/K	0.9286	likely_pathogenic	0.9251	pathogenic	-0.6	Destabilizing	0.986	D	0.743	deleterious	None	None	None	None	N
T/L	0.4192	ambiguous	0.4083	ambiguous	0.01	Stabilizing	0.953	D	0.707	prob.neutral	None	None	None	None	N
T/M	0.3127	likely_benign	0.3122	benign	0.009	Stabilizing	0.999	D	0.737	prob.delet.	None	None	None	None	N
T/N	0.7094	likely_pathogenic	0.6904	pathogenic	-1.558	Destabilizing	0.982	D	0.725	prob.delet.	N	0.463694285	None	None	N
T/P	0.9017	likely_pathogenic	0.8922	pathogenic	-0.365	Destabilizing	0.991	D	0.743	deleterious	N	0.467884567	None	None	N
T/Q	0.8687	likely_pathogenic	0.8596	pathogenic	-1.225	Destabilizing	0.993	D	0.75	deleterious	None	None	None	None	N
T/R	0.8943	likely_pathogenic	0.8889	pathogenic	-0.92	Destabilizing	0.993	D	0.756	deleterious	None	None	None	None	N
T/S	0.2357	likely_benign	0.2382	benign	-1.764	Destabilizing	0.374	N	0.481	neutral	N	0.449530431	None	None	N
T/V	0.4257	ambiguous	0.3942	ambiguous	-0.365	Destabilizing	0.91	D	0.651	neutral	None	None	None	None	N
T/W	0.9802	likely_pathogenic	0.9753	pathogenic	-1.076	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	N
T/Y	0.9171	likely_pathogenic	0.897	pathogenic	-0.674	Destabilizing	0.998	D	0.761	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.