TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19179	57760;57761;57762	chr2:178597547;178597546;178597545	chr2:179462274;179462273;179462272
N2AB	17538	52837;52838;52839	chr2:178597547;178597546;178597545	chr2:179462274;179462273;179462272
N2A	16611	50056;50057;50058	chr2:178597547;178597546;178597545	chr2:179462274;179462273;179462272
N2B	10114	30565;30566;30567	chr2:178597547;178597546;178597545	chr2:179462274;179462273;179462272
Novex-1	10239	30940;30941;30942	chr2:178597547;178597546;178597545	chr2:179462274;179462273;179462272
Novex-2	10306	31141;31142;31143	chr2:178597547;178597546;178597545	chr2:179462274;179462273;179462272
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-117
• Domain position: 85
• Structural Position: 175
• Q(SASA): 0.4411
• 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
D/N	rs1383899808	None	0.989	N	0.551	0.337	0.342631996419	gnomAD-4.0.0	6.85537E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.00314E-07	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
D/A	0.733	likely_pathogenic	0.7267	pathogenic	-0.535	Destabilizing	0.978	D	0.621	neutral	N	0.466717122	None	None	I
D/C	0.9771	likely_pathogenic	0.9749	pathogenic	-0.327	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
D/E	0.4346	ambiguous	0.3872	ambiguous	-0.743	Destabilizing	0.198	N	0.216	neutral	N	0.365187478	None	None	I
D/F	0.9693	likely_pathogenic	0.9678	pathogenic	-0.029	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
D/G	0.8536	likely_pathogenic	0.8538	pathogenic	-0.928	Destabilizing	0.989	D	0.598	neutral	N	0.486863108	None	None	I
D/H	0.7771	likely_pathogenic	0.7711	pathogenic	-0.391	Destabilizing	1.0	D	0.652	neutral	N	0.419619395	None	None	I
D/I	0.9157	likely_pathogenic	0.9057	pathogenic	0.517	Stabilizing	0.999	D	0.756	deleterious	None	None	None	None	I
D/K	0.9171	likely_pathogenic	0.9051	pathogenic	-0.58	Destabilizing	0.983	D	0.6	neutral	None	None	None	None	I
D/L	0.9052	likely_pathogenic	0.9036	pathogenic	0.517	Stabilizing	0.998	D	0.734	prob.delet.	None	None	None	None	I
D/M	0.9548	likely_pathogenic	0.9516	pathogenic	0.935	Stabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
D/N	0.4045	ambiguous	0.3954	ambiguous	-1.042	Destabilizing	0.989	D	0.551	neutral	N	0.426737369	None	None	I
D/P	0.9979	likely_pathogenic	0.9977	pathogenic	0.192	Stabilizing	0.999	D	0.668	neutral	None	None	None	None	I
D/Q	0.8327	likely_pathogenic	0.818	pathogenic	-0.858	Destabilizing	0.995	D	0.591	neutral	None	None	None	None	I
D/R	0.915	likely_pathogenic	0.9093	pathogenic	-0.423	Destabilizing	0.995	D	0.706	prob.neutral	None	None	None	None	I
D/S	0.5389	ambiguous	0.5368	ambiguous	-1.367	Destabilizing	0.983	D	0.483	neutral	None	None	None	None	I
D/T	0.7179	likely_pathogenic	0.696	pathogenic	-1.037	Destabilizing	0.998	D	0.637	neutral	None	None	None	None	I
D/V	0.7906	likely_pathogenic	0.7684	pathogenic	0.192	Stabilizing	0.997	D	0.725	prob.delet.	N	0.415405654	None	None	I
D/W	0.9907	likely_pathogenic	0.9901	pathogenic	0.115	Stabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	I
D/Y	0.818	likely_pathogenic	0.8085	pathogenic	0.209	Stabilizing	1.0	D	0.741	deleterious	N	0.468624064	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.