TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9713	29362;29363;29364	chr2:178706737;178706736;178706735	chr2:179571464;179571463;179571462
N2AB	9396	28411;28412;28413	chr2:178706737;178706736;178706735	chr2:179571464;179571463;179571462
N2A	8469	25630;25631;25632	chr2:178706737;178706736;178706735	chr2:179571464;179571463;179571462
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: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-83
• Domain position: 16
• Structural Position: 25
• Q(SASA): 0.2093
• 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	rs763317642	None	0.022	None	0.151	0.114	0.166414681773	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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	0.1821	likely_benign	0.1284	benign	-0.807	Destabilizing	0.022	N	0.151	neutral	None	None	None	None	N
T/C	0.8031	likely_pathogenic	0.7077	pathogenic	-0.538	Destabilizing	0.998	D	0.36	neutral	None	None	None	None	N
T/D	0.6988	likely_pathogenic	0.5163	ambiguous	-0.404	Destabilizing	0.842	D	0.404	neutral	None	None	None	None	N
T/E	0.5844	likely_pathogenic	0.4256	ambiguous	-0.426	Destabilizing	0.842	D	0.39	neutral	None	None	None	None	N
T/F	0.7871	likely_pathogenic	0.5951	pathogenic	-1.055	Destabilizing	0.991	D	0.44	neutral	None	None	None	None	N
T/G	0.3268	likely_benign	0.2749	benign	-1.028	Destabilizing	0.007	N	0.176	neutral	None	None	None	None	N
T/H	0.654	likely_pathogenic	0.5018	ambiguous	-1.378	Destabilizing	0.998	D	0.424	neutral	None	None	None	None	N
T/I	0.7957	likely_pathogenic	0.5917	pathogenic	-0.318	Destabilizing	0.966	D	0.357	neutral	None	None	None	None	N
T/K	0.5527	ambiguous	0.3772	ambiguous	-0.692	Destabilizing	0.842	D	0.409	neutral	None	None	None	None	N
T/L	0.4598	ambiguous	0.3008	benign	-0.318	Destabilizing	0.842	D	0.397	neutral	None	None	None	None	N
T/M	0.2029	likely_benign	0.1423	benign	0.094	Stabilizing	0.998	D	0.359	neutral	None	None	None	None	N
T/N	0.2858	likely_benign	0.1787	benign	-0.632	Destabilizing	0.801	D	0.411	neutral	None	None	None	None	N
T/P	0.9398	likely_pathogenic	0.7715	pathogenic	-0.451	Destabilizing	0.966	D	0.349	neutral	None	None	None	None	N
T/Q	0.4519	ambiguous	0.3408	ambiguous	-0.892	Destabilizing	0.974	D	0.361	neutral	None	None	None	None	N
T/R	0.5367	ambiguous	0.3233	benign	-0.402	Destabilizing	0.974	D	0.361	neutral	None	None	None	None	N
T/S	0.1622	likely_benign	0.1322	benign	-0.89	Destabilizing	0.136	N	0.186	neutral	None	None	None	None	N
T/V	0.6037	likely_pathogenic	0.4325	ambiguous	-0.451	Destabilizing	0.842	D	0.377	neutral	None	None	None	None	N
T/W	0.9466	likely_pathogenic	0.8745	pathogenic	-0.969	Destabilizing	0.998	D	0.485	neutral	None	None	None	None	N
T/Y	0.7595	likely_pathogenic	0.57	pathogenic	-0.722	Destabilizing	0.991	D	0.433	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.