TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24761	74506;74507;74508	chr2:178571851;178571850;178571849	chr2:179436578;179436577;179436576
N2AB	23120	69583;69584;69585	chr2:178571851;178571850;178571849	chr2:179436578;179436577;179436576
N2A	22193	66802;66803;66804	chr2:178571851;178571850;178571849	chr2:179436578;179436577;179436576
N2B	15696	47311;47312;47313	chr2:178571851;178571850;178571849	chr2:179436578;179436577;179436576
Novex-1	15821	47686;47687;47688	chr2:178571851;178571850;178571849	chr2:179436578;179436577;179436576
Novex-2	15888	47887;47888;47889	chr2:178571851;178571850;178571849	chr2:179436578;179436577;179436576
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-133
• Domain position: 46
• Structural Position: 115
• Q(SASA): 0.4374
• 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
R/T	rs1708301817	None	1.0	N	0.694	0.463	0.622825188919	gnomAD-4.0.0	2.0529E-06	None	None	None	None	N	None	0	0	None	3.82819E-05	0	None	0	0	1.79916E-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
R/A	0.9615	likely_pathogenic	0.9603	pathogenic	-0.801	Destabilizing	0.999	D	0.563	neutral	None	None	None	None	N
R/C	0.767	likely_pathogenic	0.792	pathogenic	-0.7	Destabilizing	1.0	D	0.668	neutral	None	None	None	None	N
R/D	0.983	likely_pathogenic	0.982	pathogenic	-0.139	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	N
R/E	0.9375	likely_pathogenic	0.9386	pathogenic	-0.018	Destabilizing	0.999	D	0.598	neutral	None	None	None	None	N
R/F	0.9814	likely_pathogenic	0.9836	pathogenic	-0.668	Destabilizing	1.0	D	0.652	neutral	None	None	None	None	N
R/G	0.9434	likely_pathogenic	0.9388	pathogenic	-1.117	Destabilizing	1.0	D	0.637	neutral	N	0.495364253	None	None	N
R/H	0.4269	ambiguous	0.4696	ambiguous	-1.411	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	N
R/I	0.9423	likely_pathogenic	0.9493	pathogenic	0.048	Stabilizing	1.0	D	0.668	neutral	D	0.522876257	None	None	N
R/K	0.5437	ambiguous	0.5601	ambiguous	-0.864	Destabilizing	0.997	D	0.474	neutral	N	0.474965366	None	None	N
R/L	0.9087	likely_pathogenic	0.9136	pathogenic	0.048	Stabilizing	1.0	D	0.637	neutral	None	None	None	None	N
R/M	0.9444	likely_pathogenic	0.9471	pathogenic	-0.208	Destabilizing	1.0	D	0.65	neutral	None	None	None	None	N
R/N	0.9605	likely_pathogenic	0.956	pathogenic	-0.309	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
R/P	0.9924	likely_pathogenic	0.9881	pathogenic	-0.214	Destabilizing	1.0	D	0.617	neutral	None	None	None	None	N
R/Q	0.5347	ambiguous	0.5454	ambiguous	-0.482	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	N
R/S	0.9678	likely_pathogenic	0.9672	pathogenic	-1.066	Destabilizing	1.0	D	0.699	prob.neutral	N	0.491338555	None	None	N
R/T	0.9257	likely_pathogenic	0.9323	pathogenic	-0.763	Destabilizing	1.0	D	0.694	prob.neutral	N	0.490021882	None	None	N
R/V	0.9568	likely_pathogenic	0.9609	pathogenic	-0.214	Destabilizing	1.0	D	0.668	neutral	None	None	None	None	N
R/W	0.7351	likely_pathogenic	0.7577	pathogenic	-0.331	Destabilizing	1.0	D	0.67	neutral	None	None	None	None	N
R/Y	0.9157	likely_pathogenic	0.9261	pathogenic	-0.029	Destabilizing	1.0	D	0.641	neutral	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.