TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27339	82240;82241;82242	chr2:178564117;178564116;178564115	chr2:179428844;179428843;179428842
N2AB	25698	77317;77318;77319	chr2:178564117;178564116;178564115	chr2:179428844;179428843;179428842
N2A	24771	74536;74537;74538	chr2:178564117;178564116;178564115	chr2:179428844;179428843;179428842
N2B	18274	55045;55046;55047	chr2:178564117;178564116;178564115	chr2:179428844;179428843;179428842
Novex-1	18399	55420;55421;55422	chr2:178564117;178564116;178564115	chr2:179428844;179428843;179428842
Novex-2	18466	55621;55622;55623	chr2:178564117;178564116;178564115	chr2:179428844;179428843;179428842
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-140
• Domain position: 62
• Structural Position: 144
• Q(SASA): 0.1286
• 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	None	None	0.999	N	0.789	0.417	0.764677420096	gnomAD-4.0.0	4.10525E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49748E-06	0	1.65667E-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
C/A	0.2642	likely_benign	0.295	benign	-1.166	Destabilizing	0.469	N	0.274	neutral	None	None	None	None	N
C/D	0.9856	likely_pathogenic	0.9885	pathogenic	-1.734	Destabilizing	0.998	D	0.825	deleterious	None	None	None	None	N
C/E	0.9949	likely_pathogenic	0.996	pathogenic	-1.561	Destabilizing	0.998	D	0.827	deleterious	None	None	None	None	N
C/F	0.8843	likely_pathogenic	0.8968	pathogenic	-1.017	Destabilizing	0.999	D	0.775	deleterious	N	0.494402516	None	None	N
C/G	0.2609	likely_benign	0.2795	benign	-1.434	Destabilizing	0.98	D	0.735	prob.delet.	N	0.490136555	None	None	N
C/H	0.9805	likely_pathogenic	0.9835	pathogenic	-1.982	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
C/I	0.7593	likely_pathogenic	0.7873	pathogenic	-0.485	Destabilizing	0.998	D	0.785	deleterious	None	None	None	None	N
C/K	0.997	likely_pathogenic	0.9975	pathogenic	-0.908	Destabilizing	0.998	D	0.814	deleterious	None	None	None	None	N
C/L	0.7963	likely_pathogenic	0.808	pathogenic	-0.485	Destabilizing	0.985	D	0.634	neutral	None	None	None	None	N
C/M	0.8966	likely_pathogenic	0.8938	pathogenic	-0.188	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
C/N	0.9162	likely_pathogenic	0.9274	pathogenic	-1.346	Destabilizing	0.999	D	0.819	deleterious	None	None	None	None	N
C/P	0.9715	likely_pathogenic	0.9728	pathogenic	-0.688	Destabilizing	0.998	D	0.825	deleterious	None	None	None	None	N
C/Q	0.985	likely_pathogenic	0.9869	pathogenic	-1.073	Destabilizing	0.999	D	0.827	deleterious	None	None	None	None	N
C/R	0.9737	likely_pathogenic	0.9779	pathogenic	-1.249	Destabilizing	0.997	D	0.813	deleterious	N	0.51301375	None	None	N
C/S	0.2545	likely_benign	0.2755	benign	-1.504	Destabilizing	0.961	D	0.671	neutral	N	0.488420546	None	None	N
C/T	0.4632	ambiguous	0.4569	ambiguous	-1.184	Destabilizing	0.985	D	0.717	prob.delet.	None	None	None	None	N
C/V	0.533	ambiguous	0.5713	pathogenic	-0.688	Destabilizing	0.985	D	0.671	neutral	None	None	None	None	N
C/W	0.9841	likely_pathogenic	0.9857	pathogenic	-1.52	Destabilizing	1.0	D	0.785	deleterious	N	0.513267239	None	None	N
C/Y	0.9588	likely_pathogenic	0.9666	pathogenic	-1.156	Destabilizing	0.999	D	0.789	deleterious	N	0.501657444	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.