TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19360	58303;58304;58305	chr2:178594416;178594415;178594414	chr2:179459143;179459142;179459141
N2AB	17719	53380;53381;53382	chr2:178594416;178594415;178594414	chr2:179459143;179459142;179459141
N2A	16792	50599;50600;50601	chr2:178594416;178594415;178594414	chr2:179459143;179459142;179459141
N2B	10295	31108;31109;31110	chr2:178594416;178594415;178594414	chr2:179459143;179459142;179459141
Novex-1	10420	31483;31484;31485	chr2:178594416;178594415;178594414	chr2:179459143;179459142;179459141
Novex-2	10487	31684;31685;31686	chr2:178594416;178594415;178594414	chr2:179459143;179459142;179459141
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-28
• Domain position: 77
• Structural Position: 109
• Q(SASA): 0.1132
• 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/N	rs761996172	-1.446	0.999	N	0.707	0.296	None	gnomAD-2.1.1	8.13E-06	None	None	None	None	N	None	6.48E-05	2.93E-05	None	0	0	None	0	None	0	0	0
S/N	rs761996172	-1.446	0.999	N	0.707	0.296	None	gnomAD-4.0.0	3.20004E-06	None	None	None	None	N	None	5.69866E-05	2.30287E-05	None	0	0	None	0	0	0	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
S/A	0.143	likely_benign	0.1122	benign	-1.344	Destabilizing	0.998	D	0.682	prob.neutral	None	None	None	None	N
S/C	0.1367	likely_benign	0.0962	benign	-1.272	Destabilizing	1.0	D	0.841	deleterious	N	0.513209055	None	None	N
S/D	0.9741	likely_pathogenic	0.9482	pathogenic	-2.311	Highly Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
S/E	0.9505	likely_pathogenic	0.9211	pathogenic	-2.104	Highly Destabilizing	0.999	D	0.682	prob.neutral	None	None	None	None	N
S/F	0.6261	likely_pathogenic	0.4726	ambiguous	-0.977	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
S/G	0.3741	ambiguous	0.2542	benign	-1.675	Destabilizing	0.999	D	0.712	prob.delet.	N	0.494739732	None	None	N
S/H	0.8084	likely_pathogenic	0.7212	pathogenic	-1.767	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
S/I	0.4245	ambiguous	0.3414	ambiguous	-0.497	Destabilizing	1.0	D	0.844	deleterious	N	0.448600216	None	None	N
S/K	0.9682	likely_pathogenic	0.9377	pathogenic	-0.782	Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	N
S/L	0.302	likely_benign	0.223	benign	-0.497	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
S/M	0.3672	ambiguous	0.3053	benign	-0.815	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
S/N	0.6997	likely_pathogenic	0.5288	ambiguous	-1.47	Destabilizing	0.999	D	0.707	prob.neutral	N	0.479255597	None	None	N
S/P	0.9967	likely_pathogenic	0.9939	pathogenic	-0.752	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
S/Q	0.8495	likely_pathogenic	0.7875	pathogenic	-1.194	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
S/R	0.9333	likely_pathogenic	0.8705	pathogenic	-1.052	Destabilizing	1.0	D	0.835	deleterious	N	0.420277464	None	None	N
S/T	0.2272	likely_benign	0.1615	benign	-1.11	Destabilizing	0.999	D	0.683	prob.neutral	N	0.478613692	None	None	N
S/V	0.4196	ambiguous	0.3323	benign	-0.752	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
S/W	0.7623	likely_pathogenic	0.6829	pathogenic	-1.309	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
S/Y	0.6165	likely_pathogenic	0.4737	ambiguous	-0.912	Destabilizing	1.0	D	0.874	deleterious	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.