TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8498	25717;25718;25719	chr2:178717242;178717241;178717240	chr2:179581969;179581968;179581967
N2AB	8181	24766;24767;24768	chr2:178717242;178717241;178717240	chr2:179581969;179581968;179581967
N2A	7254	21985;21986;21987	chr2:178717242;178717241;178717240	chr2:179581969;179581968;179581967
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: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-70
• Domain position: 43
• Structural Position: 70
• Q(SASA): 0.5551
• 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
P/A	rs1225974862	-0.136	0.001	N	0.186	0.147	0.191931220699	gnomAD-2.1.1	7.13E-06	None	None	None	None	N	None	8.27E-05	0	None	0	0	None	0	None	0	0	0
P/A	rs1225974862	-0.136	0.001	N	0.186	0.147	0.191931220699	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
P/A	rs1225974862	-0.136	0.001	N	0.186	0.147	0.191931220699	gnomAD-4.0.0	2.47906E-06	None	None	None	None	N	None	4.00673E-05	0	None	0	0	None	0	0	0	0	1.60138E-05

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
P/A	0.0919	likely_benign	0.0785	benign	-0.332	Destabilizing	0.001	N	0.186	neutral	N	0.484457521	None	None	N
P/C	0.7624	likely_pathogenic	0.7138	pathogenic	-0.635	Destabilizing	0.96	D	0.356	neutral	None	None	None	None	N
P/D	0.7409	likely_pathogenic	0.7119	pathogenic	-0.364	Destabilizing	0.067	N	0.335	neutral	None	None	None	None	N
P/E	0.5064	ambiguous	0.478	ambiguous	-0.475	Destabilizing	0.102	N	0.271	neutral	None	None	None	None	N
P/F	0.6514	likely_pathogenic	0.575	pathogenic	-0.643	Destabilizing	0.927	D	0.372	neutral	None	None	None	None	N
P/G	0.403	ambiguous	0.3387	benign	-0.433	Destabilizing	0.132	N	0.281	neutral	None	None	None	None	N
P/H	0.3393	likely_benign	0.298	benign	-0.055	Destabilizing	0.988	D	0.339	neutral	N	0.488783883	None	None	N
P/I	0.4311	ambiguous	0.3775	ambiguous	-0.211	Destabilizing	0.646	D	0.333	neutral	None	None	None	None	N
P/K	0.556	ambiguous	0.5194	ambiguous	-0.393	Destabilizing	0.784	D	0.27	neutral	None	None	None	None	N
P/L	0.1737	likely_benign	0.1433	benign	-0.211	Destabilizing	0.009	N	0.261	neutral	N	0.519879603	None	None	N
P/M	0.3914	ambiguous	0.3343	benign	-0.45	Destabilizing	0.827	D	0.34	neutral	None	None	None	None	N
P/N	0.4913	ambiguous	0.4291	ambiguous	-0.143	Destabilizing	0.312	N	0.343	neutral	None	None	None	None	N
P/Q	0.2504	likely_benign	0.215	benign	-0.361	Destabilizing	0.827	D	0.346	neutral	None	None	None	None	N
P/R	0.3845	ambiguous	0.3569	ambiguous	0.066	Stabilizing	0.906	D	0.347	neutral	D	0.523938629	None	None	N
P/S	0.1693	likely_benign	0.1456	benign	-0.442	Destabilizing	0.004	N	0.168	neutral	N	0.421155404	None	None	N
P/T	0.1245	likely_benign	0.113	benign	-0.456	Destabilizing	0.146	N	0.282	neutral	N	0.465506401	None	None	N
P/V	0.2822	likely_benign	0.2428	benign	-0.22	Destabilizing	0.242	N	0.291	neutral	None	None	None	None	N
P/W	0.7756	likely_pathogenic	0.7185	pathogenic	-0.735	Destabilizing	0.997	D	0.459	neutral	None	None	None	None	N
P/Y	0.6347	likely_pathogenic	0.5845	pathogenic	-0.433	Destabilizing	0.987	D	0.367	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.