TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14553	43882;43883;43884	chr2:178632237;178632236;178632235	chr2:179496964;179496963;179496962
N2AB	12912	38959;38960;38961	chr2:178632237;178632236;178632235	chr2:179496964;179496963;179496962
N2A	11985	36178;36179;36180	chr2:178632237;178632236;178632235	chr2:179496964;179496963;179496962
N2B	5488	16687;16688;16689	chr2:178632237;178632236;178632235	chr2:179496964;179496963;179496962
Novex-1	5613	17062;17063;17064	chr2:178632237;178632236;178632235	chr2:179496964;179496963;179496962
Novex-2	5680	17263;17264;17265	chr2:178632237;178632236;178632235	chr2:179496964;179496963;179496962
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-96
• Domain position: 57
• Structural Position: 138
• Q(SASA): 0.0417
• 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	None	None	0.022	N	0.216	0.297	0.533662478252	gnomAD-4.0.0	6.86982E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.17467E-05	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	0.8621	likely_pathogenic	0.7991	pathogenic	-2.178	Highly Destabilizing	0.688	D	0.636	neutral	None	None	None	None	N
I/C	0.9328	likely_pathogenic	0.9124	pathogenic	-1.589	Destabilizing	0.991	D	0.779	deleterious	None	None	None	None	N
I/D	0.9974	likely_pathogenic	0.9974	pathogenic	-2.623	Highly Destabilizing	0.991	D	0.839	deleterious	None	None	None	None	N
I/E	0.9921	likely_pathogenic	0.9925	pathogenic	-2.288	Highly Destabilizing	0.991	D	0.819	deleterious	None	None	None	None	N
I/F	0.5432	ambiguous	0.4614	ambiguous	-1.309	Destabilizing	0.801	D	0.657	neutral	N	0.505013708	None	None	N
I/G	0.9846	likely_pathogenic	0.9797	pathogenic	-2.807	Highly Destabilizing	0.971	D	0.809	deleterious	None	None	None	None	N
I/H	0.9869	likely_pathogenic	0.9877	pathogenic	-2.718	Highly Destabilizing	0.998	D	0.845	deleterious	None	None	None	None	N
I/K	0.975	likely_pathogenic	0.9798	pathogenic	-1.437	Destabilizing	0.915	D	0.809	deleterious	None	None	None	None	N
I/L	0.1411	likely_benign	0.1131	benign	-0.292	Destabilizing	0.002	N	0.245	neutral	N	0.237848741	None	None	N
I/M	0.2004	likely_benign	0.1631	benign	-0.619	Destabilizing	0.934	D	0.646	neutral	N	0.46496683	None	None	N
I/N	0.9667	likely_pathogenic	0.9685	pathogenic	-2.132	Highly Destabilizing	0.989	D	0.849	deleterious	N	0.504850159	None	None	N
I/P	0.9953	likely_pathogenic	0.9955	pathogenic	-0.91	Destabilizing	0.991	D	0.841	deleterious	None	None	None	None	N
I/Q	0.9804	likely_pathogenic	0.9815	pathogenic	-1.707	Destabilizing	0.991	D	0.849	deleterious	None	None	None	None	N
I/R	0.9527	likely_pathogenic	0.9623	pathogenic	-1.774	Destabilizing	0.974	D	0.841	deleterious	None	None	None	None	N
I/S	0.9527	likely_pathogenic	0.9457	pathogenic	-2.743	Highly Destabilizing	0.891	D	0.758	deleterious	N	0.504850159	None	None	N
I/T	0.9372	likely_pathogenic	0.912	pathogenic	-2.221	Highly Destabilizing	0.801	D	0.68	prob.neutral	N	0.504850159	None	None	N
I/V	0.1348	likely_benign	0.1009	benign	-0.91	Destabilizing	0.022	N	0.216	neutral	N	0.505013708	None	None	N
I/W	0.9854	likely_pathogenic	0.9835	pathogenic	-1.66	Destabilizing	0.998	D	0.839	deleterious	None	None	None	None	N
I/Y	0.9314	likely_pathogenic	0.9298	pathogenic	-1.392	Destabilizing	0.974	D	0.768	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.