TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17114	51565;51566;51567	chr2:178610186;178610185;178610184	chr2:179474913;179474912;179474911
N2AB	15473	46642;46643;46644	chr2:178610186;178610185;178610184	chr2:179474913;179474912;179474911
N2A	14546	43861;43862;43863	chr2:178610186;178610185;178610184	chr2:179474913;179474912;179474911
N2B	8049	24370;24371;24372	chr2:178610186;178610185;178610184	chr2:179474913;179474912;179474911
Novex-1	8174	24745;24746;24747	chr2:178610186;178610185;178610184	chr2:179474913;179474912;179474911
Novex-2	8241	24946;24947;24948	chr2:178610186;178610185;178610184	chr2:179474913;179474912;179474911
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-12
• Domain position: 68
• Structural Position: 100
• Q(SASA): 0.8602
• 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
N/S	None	None	0.996	N	0.544	0.276	0.250039746154	gnomAD-4.0.0	1.59277E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86143E-06	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
N/A	0.3595	ambiguous	0.3141	benign	-0.285	Destabilizing	0.997	D	0.661	neutral	None	None	None	None	N
N/C	0.4467	ambiguous	0.4209	ambiguous	0.338	Stabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
N/D	0.302	likely_benign	0.2668	benign	0.148	Stabilizing	0.998	D	0.623	neutral	N	0.469071489	None	None	N
N/E	0.6843	likely_pathogenic	0.6303	pathogenic	0.126	Stabilizing	1.0	D	0.673	neutral	None	None	None	None	N
N/F	0.7799	likely_pathogenic	0.7312	pathogenic	-0.573	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
N/G	0.2319	likely_benign	0.1951	benign	-0.48	Destabilizing	0.504	D	0.34	neutral	None	None	None	None	N
N/H	0.2245	likely_benign	0.1757	benign	-0.486	Destabilizing	1.0	D	0.701	prob.neutral	N	0.514574492	None	None	N
N/I	0.7635	likely_pathogenic	0.7674	pathogenic	0.144	Stabilizing	1.0	D	0.785	deleterious	N	0.505641965	None	None	N
N/K	0.7257	likely_pathogenic	0.6682	pathogenic	0.055	Stabilizing	0.999	D	0.681	prob.neutral	N	0.512862338	None	None	N
N/L	0.4944	ambiguous	0.4541	ambiguous	0.144	Stabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
N/M	0.6073	likely_pathogenic	0.5569	ambiguous	0.387	Stabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
N/P	0.9367	likely_pathogenic	0.9461	pathogenic	0.029	Stabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
N/Q	0.5471	ambiguous	0.4703	ambiguous	-0.34	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	N
N/R	0.704	likely_pathogenic	0.6469	pathogenic	0.078	Stabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
N/S	0.1019	likely_benign	0.0906	benign	-0.154	Destabilizing	0.996	D	0.544	neutral	N	0.496276733	None	None	N
N/T	0.3125	likely_benign	0.2948	benign	-0.03	Destabilizing	0.998	D	0.676	prob.neutral	N	0.467027145	None	None	N
N/V	0.6344	likely_pathogenic	0.6333	pathogenic	0.029	Stabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
N/W	0.9091	likely_pathogenic	0.8796	pathogenic	-0.557	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
N/Y	0.3585	ambiguous	0.3192	benign	-0.294	Destabilizing	1.0	D	0.759	deleterious	N	0.501010549	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.