TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16075	48448;48449;48450	chr2:178616568;178616567;178616566	chr2:179481295;179481294;179481293
N2AB	14434	43525;43526;43527	chr2:178616568;178616567;178616566	chr2:179481295;179481294;179481293
N2A	13507	40744;40745;40746	chr2:178616568;178616567;178616566	chr2:179481295;179481294;179481293
N2B	7010	21253;21254;21255	chr2:178616568;178616567;178616566	chr2:179481295;179481294;179481293
Novex-1	7135	21628;21629;21630	chr2:178616568;178616567;178616566	chr2:179481295;179481294;179481293
Novex-2	7202	21829;21830;21831	chr2:178616568;178616567;178616566	chr2:179481295;179481294;179481293
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-4
• Domain position: 21
• Structural Position: 23
• Q(SASA): 0.334
• 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
T/S	rs773602170	-1.521	0.022	N	0.189	0.068	0.149567049428	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
T/S	rs773602170	-1.521	0.022	N	0.189	0.068	0.149567049428	gnomAD-4.0.0	1.59408E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4339E-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
T/A	0.0828	likely_benign	0.0965	benign	-0.859	Destabilizing	0.005	N	0.181	neutral	N	0.47168355	None	None	N
T/C	0.2388	likely_benign	0.3153	benign	-0.538	Destabilizing	0.998	D	0.534	neutral	None	None	None	None	N
T/D	0.3936	ambiguous	0.4852	ambiguous	-1.423	Destabilizing	0.842	D	0.455	neutral	None	None	None	None	N
T/E	0.2757	likely_benign	0.354	ambiguous	-1.229	Destabilizing	0.842	D	0.418	neutral	None	None	None	None	N
T/F	0.1474	likely_benign	0.1809	benign	-0.402	Destabilizing	0.949	D	0.585	neutral	None	None	None	None	N
T/G	0.2098	likely_benign	0.2649	benign	-1.282	Destabilizing	0.525	D	0.484	neutral	None	None	None	None	N
T/H	0.1729	likely_benign	0.2137	benign	-1.508	Destabilizing	0.998	D	0.595	neutral	None	None	None	None	N
T/I	0.1152	likely_benign	0.1372	benign	0.248	Stabilizing	0.669	D	0.438	neutral	N	0.4806623	None	None	N
T/K	0.1723	likely_benign	0.2113	benign	-0.619	Destabilizing	0.842	D	0.424	neutral	None	None	None	None	N
T/L	0.0777	likely_benign	0.088	benign	0.248	Stabilizing	0.525	D	0.46	neutral	None	None	None	None	N
T/M	0.0802	likely_benign	0.0902	benign	0.209	Stabilizing	0.172	N	0.329	neutral	None	None	None	None	N
T/N	0.1247	likely_benign	0.1417	benign	-1.264	Destabilizing	0.801	D	0.43	neutral	N	0.473012497	None	None	N
T/P	0.6908	likely_pathogenic	0.7167	pathogenic	-0.089	Destabilizing	0.966	D	0.523	neutral	D	0.637434465	None	None	N
T/Q	0.1806	likely_benign	0.2175	benign	-0.976	Destabilizing	0.974	D	0.545	neutral	None	None	None	None	N
T/R	0.1407	likely_benign	0.169	benign	-0.883	Destabilizing	0.949	D	0.526	neutral	None	None	None	None	N
T/S	0.0863	likely_benign	0.0985	benign	-1.41	Destabilizing	0.022	N	0.189	neutral	N	0.394702946	None	None	N
T/V	0.1046	likely_benign	0.1253	benign	-0.089	Destabilizing	0.525	D	0.419	neutral	None	None	None	None	N
T/W	0.4125	ambiguous	0.5072	ambiguous	-0.694	Destabilizing	0.998	D	0.623	neutral	None	None	None	None	N
T/Y	0.1855	likely_benign	0.2309	benign	-0.292	Destabilizing	0.991	D	0.59	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.