TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35663	107212;107213;107214	chr2:178528764;178528763;178528762	chr2:179393491;179393490;179393489
N2AB	34022	102289;102290;102291	chr2:178528764;178528763;178528762	chr2:179393491;179393490;179393489
N2A	33095	99508;99509;99510	chr2:178528764;178528763;178528762	chr2:179393491;179393490;179393489
N2B	26598	80017;80018;80019	chr2:178528764;178528763;178528762	chr2:179393491;179393490;179393489
Novex-1	26723	80392;80393;80394	chr2:178528764;178528763;178528762	chr2:179393491;179393490;179393489
Novex-2	26790	80593;80594;80595	chr2:178528764;178528763;178528762	chr2:179393491;179393490;179393489
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-167
• Domain position: 57
• Structural Position: 139
• Q(SASA): 0.1467
• 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/S	None	None	0.999	N	0.526	0.458	0.33835085245	gnomAD-4.0.0	4.80129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-06	0	3.66327E-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
T/A	0.1651	likely_benign	0.1564	benign	-1.225	Destabilizing	0.999	D	0.539	neutral	N	0.485961817	None	None	N
T/C	0.737	likely_pathogenic	0.7108	pathogenic	-1.11	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
T/D	0.7219	likely_pathogenic	0.7236	pathogenic	-1.348	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
T/E	0.5261	ambiguous	0.504	ambiguous	-1.204	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
T/F	0.3546	ambiguous	0.3507	ambiguous	-0.927	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
T/G	0.6236	likely_pathogenic	0.6261	pathogenic	-1.59	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
T/H	0.4082	ambiguous	0.4044	ambiguous	-1.679	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
T/I	0.2412	likely_benign	0.2172	benign	-0.291	Destabilizing	1.0	D	0.738	prob.delet.	N	0.485441742	None	None	N
T/K	0.4404	ambiguous	0.4459	ambiguous	-0.83	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
T/L	0.1773	likely_benign	0.1705	benign	-0.291	Destabilizing	0.999	D	0.673	neutral	None	None	None	None	N
T/M	0.1348	likely_benign	0.132	benign	-0.294	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
T/N	0.2501	likely_benign	0.2609	benign	-1.288	Destabilizing	1.0	D	0.637	neutral	N	0.486655251	None	None	N
T/P	0.7676	likely_pathogenic	0.8193	pathogenic	-0.571	Destabilizing	1.0	D	0.742	deleterious	N	0.487001967	None	None	N
T/Q	0.3824	ambiguous	0.3791	ambiguous	-1.236	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
T/R	0.3474	ambiguous	0.3465	ambiguous	-0.831	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
T/S	0.2039	likely_benign	0.2094	benign	-1.543	Destabilizing	0.999	D	0.526	neutral	N	0.485961817	None	None	N
T/V	0.2231	likely_benign	0.1991	benign	-0.571	Destabilizing	0.999	D	0.581	neutral	None	None	None	None	N
T/W	0.7394	likely_pathogenic	0.7272	pathogenic	-0.952	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
T/Y	0.4097	ambiguous	0.4008	ambiguous	-0.638	Destabilizing	1.0	D	0.764	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.