TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31520	94783;94784;94785	chr2:178546870;178546869;178546868	chr2:179411597;179411596;179411595
N2AB	29879	89860;89861;89862	chr2:178546870;178546869;178546868	chr2:179411597;179411596;179411595
N2A	28952	87079;87080;87081	chr2:178546870;178546869;178546868	chr2:179411597;179411596;179411595
N2B	22455	67588;67589;67590	chr2:178546870;178546869;178546868	chr2:179411597;179411596;179411595
Novex-1	22580	67963;67964;67965	chr2:178546870;178546869;178546868	chr2:179411597;179411596;179411595
Novex-2	22647	68164;68165;68166	chr2:178546870;178546869;178546868	chr2:179411597;179411596;179411595
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-118
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.5439
• 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
R/K	rs879111902	None	0.248	N	0.134	0.142	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
R/K	rs879111902	None	0.248	N	0.134	0.142	None	gnomAD-4.0.0	3.75908E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.13764E-06	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
R/A	0.8917	likely_pathogenic	0.9176	pathogenic	-0.478	Destabilizing	0.97	D	0.695	prob.neutral	None	None	None	None	N
R/C	0.6303	likely_pathogenic	0.674	pathogenic	-0.398	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
R/D	0.9799	likely_pathogenic	0.9839	pathogenic	-0.25	Destabilizing	0.996	D	0.643	neutral	None	None	None	None	N
R/E	0.9319	likely_pathogenic	0.9409	pathogenic	-0.204	Destabilizing	0.97	D	0.639	neutral	None	None	None	None	N
R/F	0.9805	likely_pathogenic	0.9848	pathogenic	-0.79	Destabilizing	0.996	D	0.759	deleterious	None	None	None	None	N
R/G	0.7731	likely_pathogenic	0.8288	pathogenic	-0.673	Destabilizing	0.98	D	0.669	neutral	N	0.480229845	None	None	N
R/H	0.4331	ambiguous	0.4978	ambiguous	-1.075	Destabilizing	0.191	N	0.337	neutral	None	None	None	None	N
R/I	0.9588	likely_pathogenic	0.9689	pathogenic	0.006	Stabilizing	0.998	D	0.747	deleterious	N	0.490131376	None	None	N
R/K	0.2767	likely_benign	0.3082	benign	-0.468	Destabilizing	0.248	N	0.134	neutral	N	0.425357997	None	None	N
R/L	0.8849	likely_pathogenic	0.9081	pathogenic	0.006	Stabilizing	0.985	D	0.661	neutral	None	None	None	None	N
R/M	0.9412	likely_pathogenic	0.954	pathogenic	-0.068	Destabilizing	1.0	D	0.674	neutral	None	None	None	None	N
R/N	0.9561	likely_pathogenic	0.9671	pathogenic	0.033	Stabilizing	0.97	D	0.643	neutral	None	None	None	None	N
R/P	0.945	likely_pathogenic	0.9594	pathogenic	-0.136	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	N
R/Q	0.4414	ambiguous	0.5001	ambiguous	-0.266	Destabilizing	0.991	D	0.653	neutral	None	None	None	None	N
R/S	0.9249	likely_pathogenic	0.9445	pathogenic	-0.538	Destabilizing	0.961	D	0.701	prob.neutral	N	0.479437624	None	None	N
R/T	0.9403	likely_pathogenic	0.9558	pathogenic	-0.36	Destabilizing	0.98	D	0.671	neutral	N	0.506376296	None	None	N
R/V	0.957	likely_pathogenic	0.9651	pathogenic	-0.136	Destabilizing	0.996	D	0.727	prob.delet.	None	None	None	None	N
R/W	0.8519	likely_pathogenic	0.8688	pathogenic	-0.676	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
R/Y	0.9319	likely_pathogenic	0.9439	pathogenic	-0.291	Destabilizing	0.991	D	0.733	prob.delet.	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.