TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1505	4738;4739;4740	chr2:178777552;178777551;178777550	chr2:179642279;179642278;179642277
N2AB	1505	4738;4739;4740	chr2:178777552;178777551;178777550	chr2:179642279;179642278;179642277
N2A	1505	4738;4739;4740	chr2:178777552;178777551;178777550	chr2:179642279;179642278;179642277
N2B	1459	4600;4601;4602	chr2:178777552;178777551;178777550	chr2:179642279;179642278;179642277
Novex-1	1459	4600;4601;4602	chr2:178777552;178777551;178777550	chr2:179642279;179642278;179642277
Novex-2	1459	4600;4601;4602	chr2:178777552;178777551;178777550	chr2:179642279;179642278;179642277
Novex-3	1505	4738;4739;4740	chr2:178777552;178777551;178777550	chr2:179642279;179642278;179642277

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-6
• Domain position: 49
• Structural Position: 123
• Q(SASA): 0.3163
• 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
V/L	rs756907114	-0.321	0.004	N	0.261	0.084	0.508755544265	gnomAD-2.1.1	7.97E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.77E-05	0
V/L	rs756907114	-0.321	0.004	N	0.261	0.084	0.508755544265	gnomAD-4.0.0	1.43674E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79871E-05	0	1.65612E-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
V/A	0.4616	ambiguous	0.467	ambiguous	-1.507	Destabilizing	0.052	N	0.335	neutral	N	0.506840401	None	None	I
V/C	0.9349	likely_pathogenic	0.9282	pathogenic	-0.979	Destabilizing	0.935	D	0.487	neutral	None	None	None	None	I
V/D	0.8588	likely_pathogenic	0.8569	pathogenic	-1.13	Destabilizing	0.555	D	0.614	neutral	None	None	None	None	I
V/E	0.7042	likely_pathogenic	0.7017	pathogenic	-1.071	Destabilizing	0.484	N	0.559	neutral	D	0.524538714	None	None	I
V/F	0.3567	ambiguous	0.3589	ambiguous	-1.005	Destabilizing	0.38	N	0.471	neutral	None	None	None	None	I
V/G	0.6267	likely_pathogenic	0.6369	pathogenic	-1.889	Destabilizing	0.484	N	0.59	neutral	D	0.580654639	None	None	I
V/H	0.9043	likely_pathogenic	0.9081	pathogenic	-1.393	Destabilizing	0.935	D	0.645	neutral	None	None	None	None	I
V/I	0.0864	likely_benign	0.0872	benign	-0.535	Destabilizing	None	N	0.153	neutral	N	0.389791108	None	None	I
V/K	0.7955	likely_pathogenic	0.8049	pathogenic	-1.233	Destabilizing	0.555	D	0.562	neutral	None	None	None	None	I
V/L	0.286	likely_benign	0.3002	benign	-0.535	Destabilizing	0.004	N	0.261	neutral	N	0.492195058	None	None	I
V/M	0.1814	likely_benign	0.1826	benign	-0.428	Destabilizing	0.38	N	0.462	neutral	None	None	None	None	I
V/N	0.7411	likely_pathogenic	0.7449	pathogenic	-1.107	Destabilizing	0.791	D	0.637	neutral	None	None	None	None	I
V/P	0.9487	likely_pathogenic	0.9494	pathogenic	-0.824	Destabilizing	0.791	D	0.582	neutral	None	None	None	None	I
V/Q	0.7335	likely_pathogenic	0.7378	pathogenic	-1.166	Destabilizing	0.791	D	0.593	neutral	None	None	None	None	I
V/R	0.7637	likely_pathogenic	0.7726	pathogenic	-0.82	Destabilizing	0.555	D	0.635	neutral	None	None	None	None	I
V/S	0.6426	likely_pathogenic	0.6469	pathogenic	-1.717	Destabilizing	0.555	D	0.535	neutral	None	None	None	None	I
V/T	0.428	ambiguous	0.4243	ambiguous	-1.53	Destabilizing	0.149	N	0.38	neutral	None	None	None	None	I
V/W	0.9313	likely_pathogenic	0.9345	pathogenic	-1.258	Destabilizing	0.935	D	0.685	prob.neutral	None	None	None	None	I
V/Y	0.8306	likely_pathogenic	0.8254	pathogenic	-0.936	Destabilizing	0.555	D	0.483	neutral	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.