TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6503	19732;19733;19734	chr2:178728317;178728316;178728315	chr2:179593044;179593043;179593042
N2AB	6186	18781;18782;18783	chr2:178728317;178728316;178728315	chr2:179593044;179593043;179593042
N2A	5259	16000;16001;16002	chr2:178728317;178728316;178728315	chr2:179593044;179593043;179593042
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: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-49
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.3745
• 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
K/E	None	None	0.338	N	0.48	0.234	0.258283824007	gnomAD-4.0.0	1.59321E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43373E-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
K/A	0.3474	ambiguous	0.3965	ambiguous	-0.662	Destabilizing	0.404	N	0.535	neutral	None	None	None	None	N
K/C	0.7841	likely_pathogenic	0.8127	pathogenic	-0.739	Destabilizing	0.973	D	0.7	prob.neutral	None	None	None	None	N
K/D	0.5735	likely_pathogenic	0.6404	pathogenic	-0.332	Destabilizing	0.826	D	0.661	neutral	None	None	None	None	N
K/E	0.1626	likely_benign	0.1967	benign	-0.216	Destabilizing	0.338	N	0.48	neutral	N	0.493866438	None	None	N
K/F	0.743	likely_pathogenic	0.75	pathogenic	-0.373	Destabilizing	0.906	D	0.718	prob.delet.	None	None	None	None	N
K/G	0.5608	ambiguous	0.6169	pathogenic	-1.036	Destabilizing	0.575	D	0.655	neutral	None	None	None	None	N
K/H	0.314	likely_benign	0.3126	benign	-1.392	Destabilizing	0.973	D	0.684	prob.neutral	None	None	None	None	N
K/I	0.2501	likely_benign	0.2964	benign	0.311	Stabilizing	0.704	D	0.723	prob.delet.	None	None	None	None	N
K/L	0.3487	ambiguous	0.379	ambiguous	0.311	Stabilizing	0.404	N	0.645	neutral	None	None	None	None	N
K/M	0.1924	likely_benign	0.2184	benign	0.256	Stabilizing	0.965	D	0.685	prob.neutral	N	0.490077784	None	None	N
K/N	0.4021	ambiguous	0.4709	ambiguous	-0.635	Destabilizing	0.782	D	0.567	neutral	D	0.534771698	None	None	N
K/P	0.8671	likely_pathogenic	0.9	pathogenic	0.017	Stabilizing	0.906	D	0.696	prob.neutral	None	None	None	None	N
K/Q	0.1347	likely_benign	0.1473	benign	-0.728	Destabilizing	0.084	N	0.363	neutral	N	0.488556619	None	None	N
K/R	0.0877	likely_benign	0.0881	benign	-0.687	Destabilizing	0.505	D	0.461	neutral	N	0.468432062	None	None	N
K/S	0.4018	ambiguous	0.4607	ambiguous	-1.308	Destabilizing	0.404	N	0.479	neutral	None	None	None	None	N
K/T	0.1419	likely_benign	0.1711	benign	-0.982	Destabilizing	0.003	N	0.436	neutral	N	0.50862246	None	None	N
K/V	0.2569	likely_benign	0.2936	benign	0.017	Stabilizing	0.704	D	0.667	neutral	None	None	None	None	N
K/W	0.7891	likely_pathogenic	0.7716	pathogenic	-0.244	Destabilizing	0.991	D	0.677	prob.neutral	None	None	None	None	N
K/Y	0.6256	likely_pathogenic	0.6355	pathogenic	0.067	Stabilizing	0.906	D	0.718	prob.delet.	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.