TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5342	16249;16250;16251	chr2:178733269;178733268;178733267	chr2:179597996;179597995;179597994
N2AB	5025	15298;15299;15300	chr2:178733269;178733268;178733267	chr2:179597996;179597995;179597994
N2A	4098	12517;12518;12519	chr2:178733269;178733268;178733267	chr2:179597996;179597995;179597994
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: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-36
• Domain position: 82
• Structural Position: 166
• Q(SASA): 0.2963
• 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/G	None	None	0.906	N	0.361	0.294	0.28492961333	gnomAD-4.0.0	6.86201E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.01556E-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	0.0946	likely_benign	0.0976	benign	-0.722	Destabilizing	0.863	D	0.406	neutral	None	None	None	None	N
S/C	0.1298	likely_benign	0.1397	benign	-0.56	Destabilizing	0.999	D	0.455	neutral	N	0.490683214	None	None	N
S/D	0.3516	ambiguous	0.3406	ambiguous	0.312	Stabilizing	0.02	N	0.12	neutral	None	None	None	None	N
S/E	0.6109	likely_pathogenic	0.6101	pathogenic	0.276	Stabilizing	0.17	N	0.127	neutral	None	None	None	None	N
S/F	0.279	likely_benign	0.317	benign	-1.122	Destabilizing	0.997	D	0.557	neutral	None	None	None	None	N
S/G	0.1466	likely_benign	0.1538	benign	-0.905	Destabilizing	0.906	D	0.361	neutral	N	0.492569318	None	None	N
S/H	0.4683	ambiguous	0.4799	ambiguous	-1.356	Destabilizing	0.997	D	0.447	neutral	None	None	None	None	N
S/I	0.2229	likely_benign	0.2453	benign	-0.353	Destabilizing	0.996	D	0.551	neutral	D	0.523650627	None	None	N
S/K	0.8393	likely_pathogenic	0.8504	pathogenic	-0.427	Destabilizing	0.939	D	0.359	neutral	None	None	None	None	N
S/L	0.158	likely_benign	0.1697	benign	-0.353	Destabilizing	0.969	D	0.533	neutral	None	None	None	None	N
S/M	0.3317	likely_benign	0.3322	benign	-0.136	Destabilizing	0.999	D	0.441	neutral	None	None	None	None	N
S/N	0.2034	likely_benign	0.2046	benign	-0.318	Destabilizing	0.92	D	0.416	neutral	N	0.497151221	None	None	N
S/P	0.946	likely_pathogenic	0.9579	pathogenic	-0.445	Destabilizing	0.997	D	0.433	neutral	None	None	None	None	N
S/Q	0.6393	likely_pathogenic	0.6419	pathogenic	-0.508	Destabilizing	0.939	D	0.403	neutral	None	None	None	None	N
S/R	0.7411	likely_pathogenic	0.7726	pathogenic	-0.328	Destabilizing	0.976	D	0.442	neutral	D	0.534539624	None	None	N
S/T	0.1111	likely_benign	0.1183	benign	-0.448	Destabilizing	0.959	D	0.389	neutral	N	0.501851203	None	None	N
S/V	0.2167	likely_benign	0.2384	benign	-0.445	Destabilizing	0.969	D	0.535	neutral	None	None	None	None	N
S/W	0.5694	likely_pathogenic	0.6159	pathogenic	-1.034	Destabilizing	0.999	D	0.655	neutral	None	None	None	None	N
S/Y	0.2649	likely_benign	0.2885	benign	-0.767	Destabilizing	0.997	D	0.561	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.