TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18288	55087;55088;55089	chr2:178602540;178602539;178602538	chr2:179467267;179467266;179467265
N2AB	16647	50164;50165;50166	chr2:178602540;178602539;178602538	chr2:179467267;179467266;179467265
N2A	15720	47383;47384;47385	chr2:178602540;178602539;178602538	chr2:179467267;179467266;179467265
N2B	9223	27892;27893;27894	chr2:178602540;178602539;178602538	chr2:179467267;179467266;179467265
Novex-1	9348	28267;28268;28269	chr2:178602540;178602539;178602538	chr2:179467267;179467266;179467265
Novex-2	9415	28468;28469;28470	chr2:178602540;178602539;178602538	chr2:179467267;179467266;179467265
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Fn3-21
• Domain position: 17
• Structural Position: 19
• Q(SASA): 0.1464
• 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
S/C	None	None	0.965	N	0.694	0.349	0.467161347466	gnomAD-4.0.0	6.94182E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.08371E-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
S/A	0.2984	likely_benign	0.2182	benign	-0.802	Destabilizing	0.218	N	0.499	neutral	None	None	None	None	N
S/C	0.2998	likely_benign	0.1979	benign	-0.894	Destabilizing	0.965	D	0.694	prob.neutral	N	0.485902912	None	None	N
S/D	0.8857	likely_pathogenic	0.7854	pathogenic	-1.177	Destabilizing	0.404	N	0.531	neutral	None	None	None	None	N
S/E	0.9048	likely_pathogenic	0.8544	pathogenic	-1.139	Destabilizing	0.575	D	0.541	neutral	None	None	None	None	N
S/F	0.6413	likely_pathogenic	0.4073	ambiguous	-1.062	Destabilizing	0.906	D	0.772	deleterious	None	None	None	None	N
S/G	0.334	likely_benign	0.2222	benign	-1.047	Destabilizing	0.505	D	0.532	neutral	N	0.481508365	None	None	N
S/H	0.6691	likely_pathogenic	0.5369	ambiguous	-1.539	Destabilizing	0.973	D	0.704	prob.neutral	None	None	None	None	N
S/I	0.7909	likely_pathogenic	0.5956	pathogenic	-0.245	Destabilizing	0.642	D	0.755	deleterious	D	0.523503774	None	None	N
S/K	0.9587	likely_pathogenic	0.9144	pathogenic	-0.712	Destabilizing	0.575	D	0.543	neutral	None	None	None	None	N
S/L	0.4695	ambiguous	0.2819	benign	-0.245	Destabilizing	0.404	N	0.662	neutral	None	None	None	None	N
S/M	0.5218	ambiguous	0.3612	ambiguous	-0.021	Destabilizing	0.973	D	0.697	prob.neutral	None	None	None	None	N
S/N	0.5297	ambiguous	0.3394	benign	-0.935	Destabilizing	0.013	N	0.378	neutral	N	0.497548705	None	None	N
S/P	0.9953	likely_pathogenic	0.9881	pathogenic	-0.399	Destabilizing	0.906	D	0.719	prob.delet.	None	None	None	None	N
S/Q	0.8466	likely_pathogenic	0.7737	pathogenic	-1.127	Destabilizing	0.906	D	0.575	neutral	None	None	None	None	N
S/R	0.9339	likely_pathogenic	0.866	pathogenic	-0.624	Destabilizing	0.782	D	0.721	prob.delet.	N	0.482736133	None	None	N
S/T	0.1279	likely_benign	0.0846	benign	-0.825	Destabilizing	0.001	N	0.203	neutral	N	0.502632276	None	None	N
S/V	0.6823	likely_pathogenic	0.4859	ambiguous	-0.399	Destabilizing	0.404	N	0.669	neutral	None	None	None	None	N
S/W	0.7831	likely_pathogenic	0.6392	pathogenic	-1.085	Destabilizing	0.991	D	0.762	deleterious	None	None	None	None	N
S/Y	0.5584	ambiguous	0.3846	ambiguous	-0.75	Destabilizing	0.906	D	0.77	deleterious	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.