TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22085	66478;66479;66480	chr2:178582116;178582115;178582114	chr2:179446843;179446842;179446841
N2AB	20444	61555;61556;61557	chr2:178582116;178582115;178582114	chr2:179446843;179446842;179446841
N2A	19517	58774;58775;58776	chr2:178582116;178582115;178582114	chr2:179446843;179446842;179446841
N2B	13020	39283;39284;39285	chr2:178582116;178582115;178582114	chr2:179446843;179446842;179446841
Novex-1	13145	39658;39659;39660	chr2:178582116;178582115;178582114	chr2:179446843;179446842;179446841
Novex-2	13212	39859;39860;39861	chr2:178582116;178582115;178582114	chr2:179446843;179446842;179446841
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Fn3-48
• Domain position: 31
• Structural Position: 33
• Q(SASA): 0.1545
• Predicted PPI site: I

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
S/L	rs2047911570	None	0.684	N	0.661	0.376	0.514923749907	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
S/L	rs2047911570	None	0.684	N	0.661	0.376	0.514923749907	gnomAD-4.0.0	2.03012E-06	None	None	None	None	I	None	0	6.15536E-05	None	0	0	None	0	0	1.205E-06	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
S/A	0.1997	likely_benign	0.1491	benign	-0.522	Destabilizing	0.012	N	0.276	neutral	N	0.456182336	None	None	I
S/C	0.1594	likely_benign	0.0925	benign	-0.352	Destabilizing	0.996	D	0.702	prob.neutral	None	None	None	None	I
S/D	0.9549	likely_pathogenic	0.8998	pathogenic	-0.58	Destabilizing	0.742	D	0.703	prob.neutral	None	None	None	None	I
S/E	0.9528	likely_pathogenic	0.8979	pathogenic	-0.631	Destabilizing	0.59	D	0.632	neutral	None	None	None	None	I
S/F	0.6494	likely_pathogenic	0.4866	ambiguous	-0.926	Destabilizing	0.984	D	0.756	deleterious	None	None	None	None	I
S/G	0.4314	ambiguous	0.3037	benign	-0.711	Destabilizing	0.373	N	0.625	neutral	None	None	None	None	I
S/H	0.7239	likely_pathogenic	0.601	pathogenic	-1.326	Destabilizing	0.953	D	0.705	prob.neutral	None	None	None	None	I
S/I	0.758	likely_pathogenic	0.5555	ambiguous	-0.139	Destabilizing	0.91	D	0.759	deleterious	None	None	None	None	I
S/K	0.9816	likely_pathogenic	0.9519	pathogenic	-0.741	Destabilizing	0.009	N	0.405	neutral	None	None	None	None	I
S/L	0.3557	ambiguous	0.2067	benign	-0.139	Destabilizing	0.684	D	0.661	neutral	N	0.478360678	None	None	I
S/M	0.494	ambiguous	0.3552	ambiguous	0.313	Stabilizing	0.984	D	0.705	prob.neutral	None	None	None	None	I
S/N	0.4194	ambiguous	0.3054	benign	-0.607	Destabilizing	0.742	D	0.709	prob.delet.	None	None	None	None	I
S/P	0.9956	likely_pathogenic	0.992	pathogenic	-0.235	Destabilizing	0.939	D	0.717	prob.delet.	N	0.513101158	None	None	I
S/Q	0.8643	likely_pathogenic	0.7663	pathogenic	-0.89	Destabilizing	0.91	D	0.739	prob.delet.	None	None	None	None	I
S/R	0.9686	likely_pathogenic	0.9223	pathogenic	-0.52	Destabilizing	0.59	D	0.723	prob.delet.	None	None	None	None	I
S/T	0.3992	ambiguous	0.2768	benign	-0.603	Destabilizing	0.028	N	0.365	neutral	N	0.469535587	None	None	I
S/V	0.672	likely_pathogenic	0.4708	ambiguous	-0.235	Destabilizing	0.742	D	0.675	prob.neutral	None	None	None	None	I
S/W	0.8207	likely_pathogenic	0.7337	pathogenic	-0.92	Destabilizing	0.996	D	0.74	deleterious	None	None	None	None	I
S/Y	0.5698	likely_pathogenic	0.4254	ambiguous	-0.649	Destabilizing	0.984	D	0.75	deleterious	None	None	None	None	I

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.