TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7676	23251;23252;23253	chr2:178720993;178720992;178720991	chr2:179585720;179585719;179585718
N2AB	7359	22300;22301;22302	chr2:178720993;178720992;178720991	chr2:179585720;179585719;179585718
N2A	6432	19519;19520;19521	chr2:178720993;178720992;178720991	chr2:179585720;179585719;179585718
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-61
• Domain position: 69
• Structural Position: 151
• Q(SASA): 0.2443
• 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	rs199907920	-0.284	0.86	N	0.561	0.332	0.15556083564	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	3.57E-05	0
S/R	rs199907920	-0.284	0.86	N	0.561	0.332	0.15556083564	gnomAD-4.0.0	4.79697E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.4058E-06	0	1.65931E-05

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	0.0963	likely_benign	0.0992	benign	-0.993	Destabilizing	None	N	0.189	neutral	None	None	None	None	N
S/C	0.2109	likely_benign	0.215	benign	-0.681	Destabilizing	0.832	D	0.559	neutral	D	0.538821141	None	None	N
S/D	0.5627	ambiguous	0.5614	ambiguous	-0.229	Destabilizing	0.001	N	0.319	neutral	None	None	None	None	N
S/E	0.6594	likely_pathogenic	0.6592	pathogenic	-0.243	Destabilizing	0.146	N	0.439	neutral	None	None	None	None	N
S/F	0.505	ambiguous	0.4774	ambiguous	-1.357	Destabilizing	0.867	D	0.673	neutral	None	None	None	None	N
S/G	0.1104	likely_benign	0.1062	benign	-1.199	Destabilizing	0.066	N	0.453	neutral	N	0.496572244	None	None	N
S/H	0.5981	likely_pathogenic	0.5957	pathogenic	-1.642	Destabilizing	0.987	D	0.56	neutral	None	None	None	None	N
S/I	0.3743	ambiguous	0.3276	benign	-0.546	Destabilizing	0.548	D	0.636	neutral	D	0.524324511	None	None	N
S/K	0.7848	likely_pathogenic	0.7894	pathogenic	-0.633	Destabilizing	0.478	N	0.434	neutral	None	None	None	None	N
S/L	0.1964	likely_benign	0.1798	benign	-0.546	Destabilizing	0.314	N	0.585	neutral	None	None	None	None	N
S/M	0.292	likely_benign	0.2885	benign	-0.13	Destabilizing	0.961	D	0.557	neutral	None	None	None	None	N
S/N	0.236	likely_benign	0.2224	benign	-0.596	Destabilizing	0.021	N	0.459	neutral	N	0.493849992	None	None	N
S/P	0.8421	likely_pathogenic	0.8207	pathogenic	-0.665	Destabilizing	0.635	D	0.537	neutral	None	None	None	None	N
S/Q	0.6427	likely_pathogenic	0.6616	pathogenic	-0.825	Destabilizing	0.867	D	0.449	neutral	None	None	None	None	N
S/R	0.6628	likely_pathogenic	0.6759	pathogenic	-0.479	Destabilizing	0.86	D	0.561	neutral	N	0.507839644	None	None	N
S/T	0.0932	likely_benign	0.0883	benign	-0.701	Destabilizing	None	N	0.318	neutral	N	0.494165934	None	None	N
S/V	0.3627	ambiguous	0.3302	benign	-0.665	Destabilizing	0.146	N	0.577	neutral	None	None	None	None	N
S/W	0.6687	likely_pathogenic	0.6659	pathogenic	-1.25	Destabilizing	0.987	D	0.725	prob.delet.	None	None	None	None	N
S/Y	0.4768	ambiguous	0.4603	ambiguous	-0.999	Destabilizing	0.867	D	0.673	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.