TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25842	77749;77750;77751	chr2:178568608;178568607;178568606	chr2:179433335;179433334;179433333
N2AB	24201	72826;72827;72828	chr2:178568608;178568607;178568606	chr2:179433335;179433334;179433333
N2A	23274	70045;70046;70047	chr2:178568608;178568607;178568606	chr2:179433335;179433334;179433333
N2B	16777	50554;50555;50556	chr2:178568608;178568607;178568606	chr2:179433335;179433334;179433333
Novex-1	16902	50929;50930;50931	chr2:178568608;178568607;178568606	chr2:179433335;179433334;179433333
Novex-2	16969	51130;51131;51132	chr2:178568608;178568607;178568606	chr2:179433335;179433334;179433333
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-136
• Domain position: 45
• Structural Position: 109
• Q(SASA): 0.6628
• 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
T/A	rs759436335	-0.074	0.999	N	0.411	0.376	0.201204373187	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
T/A	rs759436335	-0.074	0.999	N	0.411	0.376	0.201204373187	gnomAD-4.0.0	1.59198E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43328E-05	0
T/I	None	None	1.0	N	0.565	0.394	0.31501682445	gnomAD-4.0.0	1.59198E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85976E-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
T/A	0.1646	likely_benign	0.1508	benign	-0.107	Destabilizing	0.999	D	0.411	neutral	N	0.46792419	None	None	N
T/C	0.8415	likely_pathogenic	0.8291	pathogenic	-0.293	Destabilizing	1.0	D	0.604	neutral	None	None	None	None	N
T/D	0.8085	likely_pathogenic	0.784	pathogenic	0.008	Stabilizing	1.0	D	0.574	neutral	None	None	None	None	N
T/E	0.7202	likely_pathogenic	0.6894	pathogenic	-0.082	Destabilizing	1.0	D	0.582	neutral	None	None	None	None	N
T/F	0.7525	likely_pathogenic	0.7248	pathogenic	-0.77	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	N
T/G	0.4725	ambiguous	0.4164	ambiguous	-0.17	Destabilizing	1.0	D	0.565	neutral	None	None	None	None	N
T/H	0.6832	likely_pathogenic	0.6384	pathogenic	-0.335	Destabilizing	1.0	D	0.633	neutral	None	None	None	None	N
T/I	0.5795	likely_pathogenic	0.5657	pathogenic	-0.064	Destabilizing	1.0	D	0.565	neutral	N	0.470162291	None	None	N
T/K	0.5995	likely_pathogenic	0.5717	pathogenic	-0.242	Destabilizing	1.0	D	0.582	neutral	N	0.474927521	None	None	N
T/L	0.2402	likely_benign	0.2272	benign	-0.064	Destabilizing	0.999	D	0.5	neutral	None	None	None	None	N
T/M	0.1749	likely_benign	0.1565	benign	-0.11	Destabilizing	1.0	D	0.606	neutral	None	None	None	None	N
T/N	0.3706	ambiguous	0.3132	benign	-0.018	Destabilizing	1.0	D	0.613	neutral	None	None	None	None	N
T/P	0.298	likely_benign	0.2867	benign	-0.054	Destabilizing	1.0	D	0.569	neutral	N	0.469020269	None	None	N
T/Q	0.5069	ambiguous	0.4549	ambiguous	-0.224	Destabilizing	1.0	D	0.605	neutral	None	None	None	None	N
T/R	0.5729	likely_pathogenic	0.5479	ambiguous	0.045	Stabilizing	1.0	D	0.577	neutral	N	0.49126241	None	None	N
T/S	0.2006	likely_benign	0.1758	benign	-0.174	Destabilizing	0.999	D	0.421	neutral	N	0.424151984	None	None	N
T/V	0.3681	ambiguous	0.3497	ambiguous	-0.054	Destabilizing	0.999	D	0.485	neutral	None	None	None	None	N
T/W	0.9312	likely_pathogenic	0.9194	pathogenic	-0.872	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	N
T/Y	0.7692	likely_pathogenic	0.7349	pathogenic	-0.541	Destabilizing	1.0	D	0.632	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.