TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15022	45289;45290;45291	chr2:178621858;178621857;178621856	chr2:179486585;179486584;179486583
N2AB	13381	40366;40367;40368	chr2:178621858;178621857;178621856	chr2:179486585;179486584;179486583
N2A	12454	37585;37586;37587	chr2:178621858;178621857;178621856	chr2:179486585;179486584;179486583
N2B	5957	18094;18095;18096	chr2:178621858;178621857;178621856	chr2:179486585;179486584;179486583
Novex-1	6082	18469;18470;18471	chr2:178621858;178621857;178621856	chr2:179486585;179486584;179486583
Novex-2	6149	18670;18671;18672	chr2:178621858;178621857;178621856	chr2:179486585;179486584;179486583
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-101
• Domain position: 81
• Structural Position: 166
• Q(SASA): 0.2582
• 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
G/S	rs1296403453	-0.928	1.0	N	0.705	0.416	0.168933306366	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	9.98E-05	0	None	0	None	0	0	0
G/S	rs1296403453	-0.928	1.0	N	0.705	0.416	0.168933306366	gnomAD-4.0.0	1.59509E-06	None	None	None	None	N	None	0	0	None	4.78057E-05	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
G/A	0.2744	likely_benign	0.2737	benign	-0.663	Destabilizing	1.0	D	0.642	neutral	N	0.429070932	None	None	N
G/C	0.7411	likely_pathogenic	0.7098	pathogenic	-1.235	Destabilizing	1.0	D	0.795	deleterious	N	0.496338705	None	None	N
G/D	0.9863	likely_pathogenic	0.9826	pathogenic	-1.131	Destabilizing	1.0	D	0.82	deleterious	N	0.499398165	None	None	N
G/E	0.9852	likely_pathogenic	0.9837	pathogenic	-1.075	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
G/F	0.9904	likely_pathogenic	0.9889	pathogenic	-0.88	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
G/H	0.9929	likely_pathogenic	0.991	pathogenic	-1.438	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
G/I	0.9547	likely_pathogenic	0.9609	pathogenic	0.076	Stabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
G/K	0.9921	likely_pathogenic	0.9927	pathogenic	-0.855	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
G/L	0.9665	likely_pathogenic	0.9671	pathogenic	0.076	Stabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
G/M	0.9793	likely_pathogenic	0.9796	pathogenic	-0.217	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
G/N	0.9831	likely_pathogenic	0.9814	pathogenic	-0.827	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
G/P	0.9981	likely_pathogenic	0.998	pathogenic	-0.127	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
G/Q	0.9845	likely_pathogenic	0.9829	pathogenic	-0.834	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
G/R	0.9745	likely_pathogenic	0.9713	pathogenic	-0.868	Destabilizing	1.0	D	0.834	deleterious	N	0.498213693	None	None	N
G/S	0.5496	ambiguous	0.5174	ambiguous	-1.262	Destabilizing	1.0	D	0.705	prob.neutral	N	0.442425152	None	None	N
G/T	0.8401	likely_pathogenic	0.86	pathogenic	-1.087	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
G/V	0.8581	likely_pathogenic	0.8719	pathogenic	-0.127	Destabilizing	1.0	D	0.851	deleterious	N	0.487774893	None	None	N
G/W	0.9923	likely_pathogenic	0.9894	pathogenic	-1.368	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
G/Y	0.9913	likely_pathogenic	0.9889	pathogenic	-0.836	Destabilizing	1.0	D	0.847	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.