TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18828	56707;56708;56709	chr2:178599311;178599310;178599309	chr2:179464038;179464037;179464036
N2AB	17187	51784;51785;51786	chr2:178599311;178599310;178599309	chr2:179464038;179464037;179464036
N2A	16260	49003;49004;49005	chr2:178599311;178599310;178599309	chr2:179464038;179464037;179464036
N2B	9763	29512;29513;29514	chr2:178599311;178599310;178599309	chr2:179464038;179464037;179464036
Novex-1	9888	29887;29888;29889	chr2:178599311;178599310;178599309	chr2:179464038;179464037;179464036
Novex-2	9955	30088;30089;30090	chr2:178599311;178599310;178599309	chr2:179464038;179464037;179464036
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: Fn3-24
• Domain position: 45
• Structural Position: 54
• Q(SASA): 0.709
• 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/D	None	None	0.928	N	0.419	0.242	0.227260227426	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	7.32654E-05
N/T	rs71423569	None	0.865	N	0.428	0.202	0.241078983079	gnomAD-4.0.0	6.85974E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.66091E-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	0.3006	likely_benign	0.2787	benign	-0.198	Destabilizing	0.895	D	0.415	neutral	None	None	None	None	N
N/C	0.4547	ambiguous	0.3959	ambiguous	0.284	Stabilizing	0.999	D	0.646	neutral	None	None	None	None	N
N/D	0.2161	likely_benign	0.218	benign	0.095	Stabilizing	0.928	D	0.419	neutral	N	0.443810472	None	None	N
N/E	0.556	ambiguous	0.5245	ambiguous	0.043	Stabilizing	0.944	D	0.407	neutral	None	None	None	None	N
N/F	0.6939	likely_pathogenic	0.6365	pathogenic	-0.657	Destabilizing	0.992	D	0.622	neutral	None	None	None	None	N
N/G	0.2837	likely_benign	0.2599	benign	-0.335	Destabilizing	0.895	D	0.403	neutral	None	None	None	None	N
N/H	0.1632	likely_benign	0.1409	benign	-0.346	Destabilizing	0.989	D	0.481	neutral	N	0.51086497	None	None	N
N/I	0.4205	ambiguous	0.3782	ambiguous	0.069	Stabilizing	0.989	D	0.623	neutral	N	0.514270635	None	None	N
N/K	0.4296	ambiguous	0.3935	ambiguous	0.104	Stabilizing	0.865	D	0.409	neutral	N	0.464303174	None	None	N
N/L	0.3574	ambiguous	0.3257	benign	0.069	Stabilizing	0.983	D	0.571	neutral	None	None	None	None	N
N/M	0.5024	ambiguous	0.4711	ambiguous	0.281	Stabilizing	0.999	D	0.57	neutral	None	None	None	None	N
N/P	0.6953	likely_pathogenic	0.6541	pathogenic	0.006	Stabilizing	0.992	D	0.545	neutral	None	None	None	None	N
N/Q	0.444	ambiguous	0.4074	ambiguous	-0.31	Destabilizing	0.983	D	0.457	neutral	None	None	None	None	N
N/R	0.4743	ambiguous	0.4306	ambiguous	0.183	Stabilizing	0.983	D	0.466	neutral	None	None	None	None	N
N/S	0.0945	likely_benign	0.0898	benign	-0.066	Destabilizing	0.146	N	0.287	neutral	N	0.455432975	None	None	N
N/T	0.1793	likely_benign	0.1673	benign	0.009	Stabilizing	0.865	D	0.428	neutral	N	0.483427653	None	None	N
N/V	0.3738	ambiguous	0.3374	benign	0.006	Stabilizing	0.983	D	0.609	neutral	None	None	None	None	N
N/W	0.8594	likely_pathogenic	0.8286	pathogenic	-0.707	Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	N
N/Y	0.3084	likely_benign	0.2639	benign	-0.418	Destabilizing	0.996	D	0.57	neutral	N	0.511038328	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.