TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9437	28534;28535;28536	chr2:178710788;178710787;178710786	chr2:179575515;179575514;179575513
N2AB	9120	27583;27584;27585	chr2:178710788;178710787;178710786	chr2:179575515;179575514;179575513
N2A	8193	24802;24803;24804	chr2:178710788;178710787;178710786	chr2:179575515;179575514;179575513
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: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-80
• Domain position: 41
• Structural Position: 58
• Q(SASA): 0.1548
• 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
I/T	rs1277389231	-2.713	0.801	None	0.491	0.499	0.760622118178	gnomAD-2.1.1	4.01E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	1.65289E-04
I/T	rs1277389231	-2.713	0.801	None	0.491	0.499	0.760622118178	gnomAD-4.0.0	1.59098E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02334E-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
I/A	0.9018	likely_pathogenic	0.9472	pathogenic	-2.303	Highly Destabilizing	0.067	N	0.308	neutral	None	None	None	None	N
I/C	0.9676	likely_pathogenic	0.9812	pathogenic	-1.554	Destabilizing	0.998	D	0.524	neutral	None	None	None	None	N
I/D	0.9908	likely_pathogenic	0.9956	pathogenic	-2.34	Highly Destabilizing	0.974	D	0.609	neutral	None	None	None	None	N
I/E	0.9742	likely_pathogenic	0.9842	pathogenic	-2.124	Highly Destabilizing	0.974	D	0.585	neutral	None	None	None	None	N
I/F	0.4703	ambiguous	0.5914	pathogenic	-1.421	Destabilizing	0.949	D	0.491	neutral	None	None	None	None	N
I/G	0.9676	likely_pathogenic	0.9843	pathogenic	-2.815	Highly Destabilizing	0.949	D	0.559	neutral	None	None	None	None	N
I/H	0.9738	likely_pathogenic	0.9854	pathogenic	-2.116	Highly Destabilizing	0.998	D	0.609	neutral	None	None	None	None	N
I/K	0.9445	likely_pathogenic	0.9645	pathogenic	-1.722	Destabilizing	0.966	D	0.58	neutral	None	None	None	None	N
I/L	0.1733	likely_benign	0.1789	benign	-0.835	Destabilizing	0.005	N	0.173	neutral	None	None	None	None	N
I/M	0.2201	likely_benign	0.2506	benign	-0.767	Destabilizing	0.934	D	0.515	neutral	None	None	None	None	N
I/N	0.9007	likely_pathogenic	0.9403	pathogenic	-2.021	Highly Destabilizing	0.991	D	0.632	neutral	None	None	None	None	N
I/P	0.972	likely_pathogenic	0.9862	pathogenic	-1.304	Destabilizing	0.974	D	0.617	neutral	None	None	None	None	N
I/Q	0.9546	likely_pathogenic	0.9737	pathogenic	-1.893	Destabilizing	0.991	D	0.628	neutral	None	None	None	None	N
I/R	0.9288	likely_pathogenic	0.9556	pathogenic	-1.485	Destabilizing	0.966	D	0.633	neutral	None	None	None	None	N
I/S	0.9299	likely_pathogenic	0.9624	pathogenic	-2.715	Highly Destabilizing	0.728	D	0.514	neutral	None	None	None	None	N
I/T	0.9083	likely_pathogenic	0.9444	pathogenic	-2.342	Highly Destabilizing	0.801	D	0.491	neutral	None	None	None	None	N
I/V	0.2065	likely_benign	0.2393	benign	-1.304	Destabilizing	0.012	N	0.187	neutral	None	None	None	None	N
I/W	0.967	likely_pathogenic	0.98	pathogenic	-1.691	Destabilizing	0.998	D	0.639	neutral	None	None	None	None	N
I/Y	0.8766	likely_pathogenic	0.9289	pathogenic	-1.393	Destabilizing	0.974	D	0.572	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.