TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26966	81121;81122;81123	chr2:178565236;178565235;178565234	chr2:179429963;179429962;179429961
N2AB	25325	76198;76199;76200	chr2:178565236;178565235;178565234	chr2:179429963;179429962;179429961
N2A	24398	73417;73418;73419	chr2:178565236;178565235;178565234	chr2:179429963;179429962;179429961
N2B	17901	53926;53927;53928	chr2:178565236;178565235;178565234	chr2:179429963;179429962;179429961
Novex-1	18026	54301;54302;54303	chr2:178565236;178565235;178565234	chr2:179429963;179429962;179429961
Novex-2	18093	54502;54503;54504	chr2:178565236;178565235;178565234	chr2:179429963;179429962;179429961
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-139
• Domain position: 87
• Structural Position: 173
• Q(SASA): 0.2543
• 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/R	rs1705281282	None	0.491	N	0.494	0.272	0.260249123532	gnomAD-4.0.0	3.85873E-05	None	None	None	None	N	None	6.36699E-05	0	None	0	0	None	0	0	4.08754E-05	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	0.0872	likely_benign	0.0799	benign	-0.764	Destabilizing	0.007	N	0.167	neutral	None	None	None	None	N
S/C	0.1094	likely_benign	0.0995	benign	-0.431	Destabilizing	0.987	D	0.466	neutral	N	0.503257741	None	None	N
S/D	0.3743	ambiguous	0.3301	benign	0.154	Stabilizing	0.39	N	0.361	neutral	None	None	None	None	N
S/E	0.4854	ambiguous	0.445	ambiguous	0.205	Stabilizing	0.561	D	0.363	neutral	None	None	None	None	N
S/F	0.184	likely_benign	0.1575	benign	-0.79	Destabilizing	0.901	D	0.533	neutral	None	None	None	None	N
S/G	0.1046	likely_benign	0.0978	benign	-1.059	Destabilizing	0.166	N	0.355	neutral	N	0.490887478	None	None	N
S/H	0.2845	likely_benign	0.2553	benign	-1.367	Destabilizing	0.009	N	0.333	neutral	None	None	None	None	N
S/I	0.1475	likely_benign	0.1316	benign	-0.072	Destabilizing	0.013	N	0.401	neutral	N	0.504027503	None	None	N
S/K	0.6456	likely_pathogenic	0.5912	pathogenic	-0.295	Destabilizing	0.561	D	0.354	neutral	None	None	None	None	N
S/L	0.0955	likely_benign	0.0849	benign	-0.072	Destabilizing	0.209	N	0.479	neutral	None	None	None	None	N
S/M	0.1573	likely_benign	0.1455	benign	0.007	Stabilizing	0.901	D	0.485	neutral	None	None	None	None	N
S/N	0.1049	likely_benign	0.0949	benign	-0.382	Destabilizing	0.001	N	0.179	neutral	N	0.417869956	None	None	N
S/P	0.6727	likely_pathogenic	0.695	pathogenic	-0.268	Destabilizing	0.722	D	0.495	neutral	None	None	None	None	N
S/Q	0.4527	ambiguous	0.4119	ambiguous	-0.423	Destabilizing	0.818	D	0.419	neutral	None	None	None	None	N
S/R	0.5562	ambiguous	0.5081	ambiguous	-0.351	Destabilizing	0.491	N	0.494	neutral	N	0.46589319	None	None	N
S/T	0.0683	likely_benign	0.0648	benign	-0.424	Destabilizing	0.005	N	0.163	neutral	N	0.394107662	None	None	N
S/V	0.1585	likely_benign	0.1437	benign	-0.268	Destabilizing	0.209	N	0.476	neutral	None	None	None	None	N
S/W	0.3353	likely_benign	0.3079	benign	-0.76	Destabilizing	0.991	D	0.566	neutral	None	None	None	None	N
S/Y	0.1747	likely_benign	0.1558	benign	-0.457	Destabilizing	0.692	D	0.537	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.