TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18390	55393;55394;55395	chr2:178602103;178602102;178602101	chr2:179466830;179466829;179466828
N2AB	16749	50470;50471;50472	chr2:178602103;178602102;178602101	chr2:179466830;179466829;179466828
N2A	15822	47689;47690;47691	chr2:178602103;178602102;178602101	chr2:179466830;179466829;179466828
N2B	9325	28198;28199;28200	chr2:178602103;178602102;178602101	chr2:179466830;179466829;179466828
Novex-1	9450	28573;28574;28575	chr2:178602103;178602102;178602101	chr2:179466830;179466829;179466828
Novex-2	9517	28774;28775;28776	chr2:178602103;178602102;178602101	chr2:179466830;179466829;179466828
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Ig-115
• Domain position: 9
• Structural Position: 16
• Q(SASA): 0.1405
• 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
C/Y	rs759877537	-1.388	0.794	N	0.695	0.354	0.658123265804	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	6.48E-05	0	None	0	0	None	0	None	0	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
C/A	0.5139	ambiguous	0.4652	ambiguous	-1.796	Destabilizing	0.061	N	0.45	neutral	None	None	None	None	N
C/D	0.9562	likely_pathogenic	0.9489	pathogenic	-0.777	Destabilizing	0.94	D	0.72	prob.delet.	None	None	None	None	N
C/E	0.9488	likely_pathogenic	0.9384	pathogenic	-0.661	Destabilizing	0.836	D	0.722	prob.delet.	None	None	None	None	N
C/F	0.3565	ambiguous	0.3376	benign	-1.186	Destabilizing	0.655	D	0.7	prob.neutral	N	0.461831377	None	None	N
C/G	0.4502	ambiguous	0.4223	ambiguous	-2.115	Highly Destabilizing	0.523	D	0.681	prob.neutral	N	0.475742037	None	None	N
C/H	0.8273	likely_pathogenic	0.8014	pathogenic	-2.219	Highly Destabilizing	0.983	D	0.691	prob.neutral	None	None	None	None	N
C/I	0.4322	ambiguous	0.3945	ambiguous	-0.969	Destabilizing	0.004	N	0.374	neutral	None	None	None	None	N
C/K	0.938	likely_pathogenic	0.9284	pathogenic	-1.2	Destabilizing	0.836	D	0.719	prob.delet.	None	None	None	None	N
C/L	0.5116	ambiguous	0.479	ambiguous	-0.969	Destabilizing	0.061	N	0.469	neutral	None	None	None	None	N
C/M	0.6647	likely_pathogenic	0.625	pathogenic	0.028	Stabilizing	0.716	D	0.711	prob.delet.	None	None	None	None	N
C/N	0.8586	likely_pathogenic	0.8353	pathogenic	-1.242	Destabilizing	0.94	D	0.735	prob.delet.	None	None	None	None	N
C/P	0.9845	likely_pathogenic	0.9863	pathogenic	-1.219	Destabilizing	0.94	D	0.723	prob.delet.	None	None	None	None	N
C/Q	0.8528	likely_pathogenic	0.8313	pathogenic	-1.133	Destabilizing	0.94	D	0.736	prob.delet.	None	None	None	None	N
C/R	0.7826	likely_pathogenic	0.7675	pathogenic	-1.103	Destabilizing	0.794	D	0.736	prob.delet.	N	0.505371511	None	None	N
C/S	0.5359	ambiguous	0.4917	ambiguous	-1.748	Destabilizing	0.351	N	0.597	neutral	N	0.505024794	None	None	N
C/T	0.5744	likely_pathogenic	0.5192	ambiguous	-1.45	Destabilizing	0.228	N	0.574	neutral	None	None	None	None	N
C/V	0.302	likely_benign	0.2841	benign	-1.219	Destabilizing	None	N	0.387	neutral	None	None	None	None	N
C/W	0.7755	likely_pathogenic	0.765	pathogenic	-1.238	Destabilizing	0.978	D	0.663	neutral	N	0.505718227	None	None	N
C/Y	0.557	ambiguous	0.5304	ambiguous	-1.202	Destabilizing	0.794	D	0.695	prob.neutral	N	0.486516391	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.