TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23390	70393;70394;70395	chr2:178575964;178575963;178575962	chr2:179440691;179440690;179440689
N2AB	21749	65470;65471;65472	chr2:178575964;178575963;178575962	chr2:179440691;179440690;179440689
N2A	20822	62689;62690;62691	chr2:178575964;178575963;178575962	chr2:179440691;179440690;179440689
N2B	14325	43198;43199;43200	chr2:178575964;178575963;178575962	chr2:179440691;179440690;179440689
Novex-1	14450	43573;43574;43575	chr2:178575964;178575963;178575962	chr2:179440691;179440690;179440689
Novex-2	14517	43774;43775;43776	chr2:178575964;178575963;178575962	chr2:179440691;179440690;179440689
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-129
• Domain position: 46
• Structural Position: 122
• Q(SASA): 0.7124
• 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/H	None	None	None	N	0.144	0.12	0.233150807113	gnomAD-4.0.0	1.59651E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.87219E-06	0	0
N/S	rs747202126	0.142	0.005	N	0.164	0.13	0.163833314356	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
N/S	rs747202126	0.142	0.005	N	0.164	0.13	0.163833314356	gnomAD-4.0.0	2.05553E-06	None	None	None	None	N	None	2.99204E-05	0	None	0	0	None	0	0	9.00844E-07	1.16025E-05	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	0.1444	likely_benign	0.1629	benign	-0.473	Destabilizing	0.209	N	0.342	neutral	None	None	None	None	N
N/C	0.199	likely_benign	0.2161	benign	0.137	Stabilizing	0.991	D	0.352	neutral	None	None	None	None	N
N/D	0.1443	likely_benign	0.1644	benign	0.182	Stabilizing	0.285	N	0.245	neutral	N	0.438802589	None	None	N
N/E	0.3285	likely_benign	0.3852	ambiguous	0.221	Stabilizing	0.345	N	0.229	neutral	None	None	None	None	N
N/F	0.3635	ambiguous	0.4036	ambiguous	-0.504	Destabilizing	0.901	D	0.371	neutral	None	None	None	None	N
N/G	0.2555	likely_benign	0.2759	benign	-0.738	Destabilizing	0.209	N	0.255	neutral	None	None	None	None	N
N/H	0.0925	likely_benign	0.0953	benign	-0.527	Destabilizing	None	N	0.144	neutral	N	0.409423831	None	None	N
N/I	0.1229	likely_benign	0.1352	benign	0.16	Stabilizing	0.873	D	0.379	neutral	N	0.430337821	None	None	N
N/K	0.2994	likely_benign	0.3352	benign	0.026	Stabilizing	0.285	N	0.213	neutral	N	0.411767916	None	None	N
N/L	0.1738	likely_benign	0.1808	benign	0.16	Stabilizing	0.561	D	0.383	neutral	None	None	None	None	N
N/M	0.2169	likely_benign	0.2358	benign	0.317	Stabilizing	0.965	D	0.345	neutral	None	None	None	None	N
N/P	0.8213	likely_pathogenic	0.8481	pathogenic	-0.021	Destabilizing	0.722	D	0.377	neutral	None	None	None	None	N
N/Q	0.2622	likely_benign	0.2822	benign	-0.481	Destabilizing	0.561	D	0.263	neutral	None	None	None	None	N
N/R	0.3085	likely_benign	0.3523	ambiguous	0.021	Stabilizing	0.561	D	0.19	neutral	None	None	None	None	N
N/S	0.0724	likely_benign	0.0746	benign	-0.454	Destabilizing	0.005	N	0.164	neutral	N	0.423851779	None	None	N
N/T	0.0815	likely_benign	0.0896	benign	-0.237	Destabilizing	0.166	N	0.213	neutral	N	0.42947103	None	None	N
N/V	0.118	likely_benign	0.1281	benign	-0.021	Destabilizing	0.561	D	0.393	neutral	None	None	None	None	N
N/W	0.679	likely_pathogenic	0.7226	pathogenic	-0.373	Destabilizing	0.991	D	0.38	neutral	None	None	None	None	N
N/Y	0.1387	likely_benign	0.1524	benign	-0.128	Destabilizing	0.491	N	0.373	neutral	N	0.482940155	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.