TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31694	95305;95306;95307	chr2:178546251;178546250;178546249	chr2:179410978;179410977;179410976
N2AB	30053	90382;90383;90384	chr2:178546251;178546250;178546249	chr2:179410978;179410977;179410976
N2A	29126	87601;87602;87603	chr2:178546251;178546250;178546249	chr2:179410978;179410977;179410976
N2B	22629	68110;68111;68112	chr2:178546251;178546250;178546249	chr2:179410978;179410977;179410976
Novex-1	22754	68485;68486;68487	chr2:178546251;178546250;178546249	chr2:179410978;179410977;179410976
Novex-2	22821	68686;68687;68688	chr2:178546251;178546250;178546249	chr2:179410978;179410977;179410976
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-152
• Domain position: 74
• Structural Position: 163
• Q(SASA): 0.742
• Predicted PPI site: I

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	rs776679937	0.082	1.0	N	0.698	0.461	0.321672782286	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.9E-06	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	0.1037	likely_benign	0.1003	benign	-0.288	Destabilizing	0.998	D	0.632	neutral	None	None	None	None	I
S/C	0.105	likely_benign	0.121	benign	-0.525	Destabilizing	1.0	D	0.704	prob.neutral	N	0.516359295	None	None	I
S/D	0.9282	likely_pathogenic	0.9381	pathogenic	-0.344	Destabilizing	0.999	D	0.664	neutral	None	None	None	None	I
S/E	0.9423	likely_pathogenic	0.9478	pathogenic	-0.45	Destabilizing	0.999	D	0.664	neutral	None	None	None	None	I
S/F	0.4825	ambiguous	0.5192	ambiguous	-1.04	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	I
S/G	0.1802	likely_benign	0.1771	benign	-0.28	Destabilizing	0.999	D	0.58	neutral	N	0.500427051	None	None	I
S/H	0.7553	likely_pathogenic	0.7996	pathogenic	-0.506	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
S/I	0.4462	ambiguous	0.438	ambiguous	-0.417	Destabilizing	1.0	D	0.724	prob.delet.	N	0.509681252	None	None	I
S/K	0.9782	likely_pathogenic	0.9809	pathogenic	-0.509	Destabilizing	0.999	D	0.665	neutral	None	None	None	None	I
S/L	0.2412	likely_benign	0.2562	benign	-0.417	Destabilizing	1.0	D	0.642	neutral	None	None	None	None	I
S/M	0.3836	ambiguous	0.3979	ambiguous	-0.345	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
S/N	0.4733	ambiguous	0.5472	ambiguous	-0.28	Destabilizing	0.999	D	0.663	neutral	N	0.492482358	None	None	I
S/P	0.9338	likely_pathogenic	0.9185	pathogenic	-0.357	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	I
S/Q	0.8799	likely_pathogenic	0.8927	pathogenic	-0.491	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
S/R	0.9497	likely_pathogenic	0.9571	pathogenic	-0.263	Destabilizing	1.0	D	0.698	prob.neutral	N	0.490429724	None	None	I
S/T	0.2405	likely_benign	0.2082	benign	-0.414	Destabilizing	0.999	D	0.575	neutral	N	0.504947436	None	None	I
S/V	0.3691	ambiguous	0.3488	ambiguous	-0.357	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
S/W	0.6878	likely_pathogenic	0.7271	pathogenic	-1.135	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	I
S/Y	0.497	ambiguous	0.5535	ambiguous	-0.844	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	I

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.