TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5815	17668;17669;17670	chr2:178731323;178731322;178731321	chr2:179596050;179596049;179596048
N2AB	5498	16717;16718;16719	chr2:178731323;178731322;178731321	chr2:179596050;179596049;179596048
N2A	4571	13936;13937;13938	chr2:178731323;178731322;178731321	chr2:179596050;179596049;179596048
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-41
• Domain position: 86
• Structural Position: 172
• Q(SASA): 0.0861
• 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
A/G	None	None	1.0	N	0.591	0.525	0.530606565545	gnomAD-4.0.0	6.84241E-07	None	None	None	None	N	None	0	0	None	0	0	None	1.87371E-05	0	0	0	0
A/T	rs987166734	None	1.0	N	0.711	0.536	0.511790803624	gnomAD-4.0.0	1.59146E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85866E-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
A/C	0.799	likely_pathogenic	0.8251	pathogenic	-0.84	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
A/D	0.9701	likely_pathogenic	0.9666	pathogenic	-0.84	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
A/E	0.9777	likely_pathogenic	0.9735	pathogenic	-0.752	Destabilizing	1.0	D	0.85	deleterious	D	0.538317843	None	None	N
A/F	0.9393	likely_pathogenic	0.9457	pathogenic	-0.64	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
A/G	0.1973	likely_benign	0.2111	benign	-1.144	Destabilizing	1.0	D	0.591	neutral	N	0.506223937	None	None	N
A/H	0.981	likely_pathogenic	0.9827	pathogenic	-1.368	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
A/I	0.9117	likely_pathogenic	0.9174	pathogenic	0.189	Stabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
A/K	0.9933	likely_pathogenic	0.9916	pathogenic	-0.819	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
A/L	0.8275	likely_pathogenic	0.8336	pathogenic	0.189	Stabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
A/M	0.8491	likely_pathogenic	0.8652	pathogenic	0.006	Stabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
A/N	0.9406	likely_pathogenic	0.9471	pathogenic	-0.799	Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
A/P	0.9918	likely_pathogenic	0.9903	pathogenic	-0.082	Destabilizing	1.0	D	0.883	deleterious	D	0.538571333	None	None	N
A/Q	0.964	likely_pathogenic	0.9614	pathogenic	-0.743	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
A/R	0.9822	likely_pathogenic	0.9764	pathogenic	-0.804	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
A/S	0.1745	likely_benign	0.2003	benign	-1.322	Destabilizing	1.0	D	0.613	neutral	N	0.497550203	None	None	N
A/T	0.4041	ambiguous	0.4428	ambiguous	-1.101	Destabilizing	1.0	D	0.711	prob.delet.	N	0.51029886	None	None	N
A/V	0.6653	likely_pathogenic	0.6756	pathogenic	-0.082	Destabilizing	1.0	D	0.649	neutral	N	0.488392263	None	None	N
A/W	0.9953	likely_pathogenic	0.9958	pathogenic	-1.154	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
A/Y	0.977	likely_pathogenic	0.979	pathogenic	-0.617	Destabilizing	1.0	D	0.889	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.