TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5410	16453;16454;16455	chr2:178732948;178732947;178732946	chr2:179597675;179597674;179597673
N2AB	5093	15502;15503;15504	chr2:178732948;178732947;178732946	chr2:179597675;179597674;179597673
N2A	4166	12721;12722;12723	chr2:178732948;178732947;178732946	chr2:179597675;179597674;179597673
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: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-37
• Domain position: 54
• Structural Position: 134
• Q(SASA): 0.1749
• 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
G/C	None	None	1.0	D	0.707	0.505	0.786423769647	gnomAD-4.0.0	6.84302E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99496E-07	0	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
G/A	0.3384	likely_benign	0.3074	benign	-0.489	Destabilizing	0.835	D	0.555	neutral	N	0.489224729	None	None	N
G/C	0.5969	likely_pathogenic	0.5327	ambiguous	-0.759	Destabilizing	1.0	D	0.707	prob.neutral	D	0.545364827	None	None	N
G/D	0.4305	ambiguous	0.3208	benign	-0.752	Destabilizing	0.071	N	0.433	neutral	D	0.524399989	None	None	N
G/E	0.5027	ambiguous	0.3978	ambiguous	-0.827	Destabilizing	0.942	D	0.621	neutral	None	None	None	None	N
G/F	0.9021	likely_pathogenic	0.8827	pathogenic	-0.883	Destabilizing	0.996	D	0.721	prob.delet.	None	None	None	None	N
G/H	0.7448	likely_pathogenic	0.6723	pathogenic	-1.066	Destabilizing	0.351	N	0.594	neutral	None	None	None	None	N
G/I	0.8182	likely_pathogenic	0.7983	pathogenic	-0.205	Destabilizing	0.996	D	0.717	prob.delet.	None	None	None	None	N
G/K	0.822	likely_pathogenic	0.7555	pathogenic	-1.077	Destabilizing	0.991	D	0.629	neutral	None	None	None	None	N
G/L	0.8501	likely_pathogenic	0.8261	pathogenic	-0.205	Destabilizing	0.996	D	0.677	prob.neutral	None	None	None	None	N
G/M	0.8077	likely_pathogenic	0.7777	pathogenic	-0.24	Destabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	N
G/N	0.3707	ambiguous	0.3029	benign	-0.744	Destabilizing	0.97	D	0.594	neutral	None	None	None	None	N
G/P	0.978	likely_pathogenic	0.9729	pathogenic	-0.259	Destabilizing	0.996	D	0.689	prob.neutral	None	None	None	None	N
G/Q	0.6379	likely_pathogenic	0.5598	ambiguous	-0.912	Destabilizing	0.996	D	0.695	prob.neutral	None	None	None	None	N
G/R	0.7272	likely_pathogenic	0.6433	pathogenic	-0.767	Destabilizing	0.989	D	0.691	prob.neutral	N	0.501545767	None	None	N
G/S	0.2004	likely_benign	0.1708	benign	-0.981	Destabilizing	0.489	N	0.328	neutral	D	0.533904906	None	None	N
G/T	0.4854	ambiguous	0.4376	ambiguous	-0.97	Destabilizing	0.942	D	0.626	neutral	None	None	None	None	N
G/V	0.6657	likely_pathogenic	0.6374	pathogenic	-0.259	Destabilizing	0.994	D	0.695	prob.neutral	N	0.521473674	None	None	N
G/W	0.813	likely_pathogenic	0.7662	pathogenic	-1.236	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
G/Y	0.7452	likely_pathogenic	0.6867	pathogenic	-0.804	Destabilizing	0.991	D	0.719	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.