TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5582	16969;16970;16971	chr2:178732225;178732224;178732223	chr2:179596952;179596951;179596950
N2AB	5265	16018;16019;16020	chr2:178732225;178732224;178732223	chr2:179596952;179596951;179596950
N2A	4338	13237;13238;13239	chr2:178732225;178732224;178732223	chr2:179596952;179596951;179596950
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: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-39
• Domain position: 40
• Structural Position: 55
• Q(SASA): 0.5005
• 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
R/G	None	None	0.837	N	0.359	0.318	0.522611632499	gnomAD-4.0.0	1.59119E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85816E-06	0	0
R/I	rs1232658661	None	0.719	N	0.424	0.309	0.602640947006	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
R/I	rs1232658661	None	0.719	N	0.424	0.309	0.602640947006	gnomAD-4.0.0	6.57125E-06	None	None	None	None	N	None	0	6.54707E-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
R/A	0.2176	likely_benign	0.2545	benign	0.072	Stabilizing	0.737	D	0.369	neutral	None	None	None	None	N
R/C	0.1549	likely_benign	0.1687	benign	-0.005	Destabilizing	0.998	D	0.338	neutral	None	None	None	None	N
R/D	0.3791	ambiguous	0.4306	ambiguous	-0.126	Destabilizing	0.773	D	0.407	neutral	None	None	None	None	N
R/E	0.191	likely_benign	0.2103	benign	-0.067	Destabilizing	0.872	D	0.293	neutral	None	None	None	None	N
R/F	0.356	ambiguous	0.3929	ambiguous	-0.142	Destabilizing	0.96	D	0.381	neutral	None	None	None	None	N
R/G	0.1534	likely_benign	0.1772	benign	-0.119	Destabilizing	0.837	D	0.359	neutral	N	0.487479183	None	None	N
R/H	0.0838	likely_benign	0.091	benign	-0.65	Destabilizing	0.98	D	0.338	neutral	None	None	None	None	N
R/I	0.1421	likely_benign	0.1585	benign	0.537	Stabilizing	0.719	D	0.424	neutral	N	0.488556619	None	None	N
R/K	0.0845	likely_benign	0.0914	benign	0.011	Stabilizing	0.679	D	0.354	neutral	N	0.431815114	None	None	N
R/L	0.1708	likely_benign	0.1919	benign	0.537	Stabilizing	0.584	D	0.364	neutral	None	None	None	None	N
R/M	0.1545	likely_benign	0.1737	benign	0.119	Stabilizing	0.209	N	0.281	neutral	None	None	None	None	N
R/N	0.3177	likely_benign	0.3696	ambiguous	0.262	Stabilizing	0.083	N	0.255	neutral	None	None	None	None	N
R/P	0.8447	likely_pathogenic	0.8712	pathogenic	0.402	Stabilizing	0.993	D	0.379	neutral	None	None	None	None	N
R/Q	0.0815	likely_benign	0.0869	benign	0.164	Stabilizing	0.932	D	0.343	neutral	None	None	None	None	N
R/S	0.2628	likely_benign	0.3062	benign	-0.029	Destabilizing	0.514	D	0.368	neutral	N	0.456537414	None	None	N
R/T	0.1177	likely_benign	0.1348	benign	0.156	Stabilizing	0.064	N	0.247	neutral	N	0.42806552	None	None	N
R/V	0.1964	likely_benign	0.2212	benign	0.402	Stabilizing	0.584	D	0.368	neutral	None	None	None	None	N
R/W	0.1404	likely_benign	0.15	benign	-0.227	Destabilizing	0.998	D	0.34	neutral	None	None	None	None	N
R/Y	0.2669	likely_benign	0.2966	benign	0.181	Stabilizing	0.993	D	0.373	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.