TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9546	28861;28862;28863	chr2:178709683;178709682;178709681	chr2:179574410;179574409;179574408
N2AB	9229	27910;27911;27912	chr2:178709683;178709682;178709681	chr2:179574410;179574409;179574408
N2A	8302	25129;25130;25131	chr2:178709683;178709682;178709681	chr2:179574410;179574409;179574408
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: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-81
• Domain position: 54
• Structural Position: 131
• Q(SASA): 0.6513
• 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/K	None	None	0.801	None	0.298	0.121	0.107399877778	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
N/S	None	None	0.062	None	0.112	0.092	0.0846915920261	gnomAD-4.0.0	1.59105E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85791E-06	0	0
N/Y	None	None	0.989	None	0.311	0.296	0.407767136052	gnomAD-4.0.0	4.80129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-06	0	3.66327E-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
N/A	0.4331	ambiguous	0.4152	ambiguous	-0.087	Destabilizing	0.525	D	0.33	neutral	None	None	None	None	N
N/C	0.6112	likely_pathogenic	0.6089	pathogenic	0.106	Stabilizing	0.998	D	0.338	neutral	None	None	None	None	N
N/D	0.1525	likely_benign	0.1421	benign	0.09	Stabilizing	0.005	N	0.1	neutral	None	None	None	None	N
N/E	0.4746	ambiguous	0.4496	ambiguous	0.024	Stabilizing	0.525	D	0.31	neutral	None	None	None	None	N
N/F	0.8222	likely_pathogenic	0.7904	pathogenic	-0.724	Destabilizing	0.991	D	0.328	neutral	None	None	None	None	N
N/G	0.3184	likely_benign	0.2905	benign	-0.164	Destabilizing	0.688	D	0.343	neutral	None	None	None	None	N
N/H	0.1861	likely_benign	0.1732	benign	-0.183	Destabilizing	0.989	D	0.303	neutral	None	None	None	None	N
N/I	0.6391	likely_pathogenic	0.6285	pathogenic	0.013	Stabilizing	0.966	D	0.355	neutral	None	None	None	None	N
N/K	0.4456	ambiguous	0.407	ambiguous	0.1	Stabilizing	0.801	D	0.298	neutral	None	None	None	None	N
N/L	0.5632	ambiguous	0.5499	ambiguous	0.013	Stabilizing	0.915	D	0.378	neutral	None	None	None	None	N
N/M	0.6039	likely_pathogenic	0.5788	pathogenic	0.066	Stabilizing	0.998	D	0.313	neutral	None	None	None	None	N
N/P	0.8642	likely_pathogenic	0.8644	pathogenic	0.002	Stabilizing	0.974	D	0.351	neutral	None	None	None	None	N
N/Q	0.4282	ambiguous	0.4127	ambiguous	-0.278	Destabilizing	0.974	D	0.279	neutral	None	None	None	None	N
N/R	0.5421	ambiguous	0.4934	ambiguous	0.161	Stabilizing	0.974	D	0.277	neutral	None	None	None	None	N
N/S	0.1343	likely_benign	0.1323	benign	-0.061	Destabilizing	0.062	N	0.112	neutral	None	None	None	None	N
N/T	0.3089	likely_benign	0.3056	benign	-0.019	Destabilizing	0.669	D	0.3	neutral	None	None	None	None	N
N/V	0.6368	likely_pathogenic	0.6258	pathogenic	0.002	Stabilizing	0.974	D	0.361	neutral	None	None	None	None	N
N/W	0.898	likely_pathogenic	0.8833	pathogenic	-0.877	Destabilizing	0.998	D	0.494	neutral	None	None	None	None	N
N/Y	0.2919	likely_benign	0.264	benign	-0.544	Destabilizing	0.989	D	0.311	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.