TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17024	51295;51296;51297	chr2:178611059;178611058;178611057	chr2:179475786;179475785;179475784
N2AB	15383	46372;46373;46374	chr2:178611059;178611058;178611057	chr2:179475786;179475785;179475784
N2A	14456	43591;43592;43593	chr2:178611059;178611058;178611057	chr2:179475786;179475785;179475784
N2B	7959	24100;24101;24102	chr2:178611059;178611058;178611057	chr2:179475786;179475785;179475784
Novex-1	8084	24475;24476;24477	chr2:178611059;178611058;178611057	chr2:179475786;179475785;179475784
Novex-2	8151	24676;24677;24678	chr2:178611059;178611058;178611057	chr2:179475786;179475785;179475784
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-111
• Domain position: 70
• Structural Position: 153
• Q(SASA): 0.3541
• 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
I/S	rs1389981053	-1.714	0.003	N	0.303	0.141	0.646007317467	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
I/S	rs1389981053	-1.714	0.003	N	0.303	0.141	0.646007317467	gnomAD-4.0.0	3.18653E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.86722E-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
I/A	0.1868	likely_benign	0.163	benign	-1.552	Destabilizing	0.002	N	0.295	neutral	None	None	None	None	N
I/C	0.4607	ambiguous	0.4157	ambiguous	-1.053	Destabilizing	0.245	N	0.468	neutral	None	None	None	None	N
I/D	0.3409	ambiguous	0.2954	benign	-0.543	Destabilizing	0.009	N	0.337	neutral	None	None	None	None	N
I/E	0.2737	likely_benign	0.235	benign	-0.544	Destabilizing	0.004	N	0.338	neutral	None	None	None	None	N
I/F	0.1384	likely_benign	0.1235	benign	-1.196	Destabilizing	0.033	N	0.389	neutral	N	0.497213295	None	None	N
I/G	0.3773	ambiguous	0.3202	benign	-1.861	Destabilizing	0.008	N	0.329	neutral	None	None	None	None	N
I/H	0.2714	likely_benign	0.2412	benign	-1.063	Destabilizing	0.245	N	0.535	neutral	None	None	None	None	N
I/K	0.1676	likely_benign	0.1533	benign	-0.799	Destabilizing	0.009	N	0.333	neutral	None	None	None	None	N
I/L	0.0955	likely_benign	0.0925	benign	-0.788	Destabilizing	0.001	N	0.195	neutral	N	0.459570333	None	None	N
I/M	0.0918	likely_benign	0.0837	benign	-0.621	Destabilizing	0.033	N	0.47	neutral	N	0.486499235	None	None	N
I/N	0.1073	likely_benign	0.0917	benign	-0.595	Destabilizing	None	N	0.357	neutral	N	0.451106007	None	None	N
I/P	0.5708	likely_pathogenic	0.5036	ambiguous	-1.011	Destabilizing	0.22	N	0.502	neutral	None	None	None	None	N
I/Q	0.2003	likely_benign	0.179	benign	-0.775	Destabilizing	None	N	0.328	neutral	None	None	None	None	N
I/R	0.1524	likely_benign	0.1372	benign	-0.289	Destabilizing	0.018	N	0.437	neutral	None	None	None	None	N
I/S	0.1421	likely_benign	0.1267	benign	-1.324	Destabilizing	0.003	N	0.303	neutral	N	0.464832961	None	None	N
I/T	0.1104	likely_benign	0.1007	benign	-1.201	Destabilizing	None	N	0.156	neutral	N	0.410754375	None	None	N
I/V	0.0667	likely_benign	0.0618	benign	-1.011	Destabilizing	None	N	0.103	neutral	N	0.410266758	None	None	N
I/W	0.6741	likely_pathogenic	0.6247	pathogenic	-1.205	Destabilizing	0.788	D	0.513	neutral	None	None	None	None	N
I/Y	0.3418	ambiguous	0.3121	benign	-0.961	Destabilizing	0.085	N	0.469	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.