TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14458	43597;43598;43599	chr2:178632634;178632633;178632632	chr2:179497361;179497360;179497359
N2AB	12817	38674;38675;38676	chr2:178632634;178632633;178632632	chr2:179497361;179497360;179497359
N2A	11890	35893;35894;35895	chr2:178632634;178632633;178632632	chr2:179497361;179497360;179497359
N2B	5393	16402;16403;16404	chr2:178632634;178632633;178632632	chr2:179497361;179497360;179497359
Novex-1	5518	16777;16778;16779	chr2:178632634;178632633;178632632	chr2:179497361;179497360;179497359
Novex-2	5585	16978;16979;16980	chr2:178632634;178632633;178632632	chr2:179497361;179497360;179497359
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-95
• Domain position: 51
• Structural Position: 130
• Q(SASA): 0.478
• 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
D/E	None	None	0.006	N	0.218	0.264	0.376216005999	gnomAD-4.0.0	5.47445E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.19673E-06	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
D/A	0.1399	likely_benign	0.1366	benign	-0.187	Destabilizing	0.698	D	0.411	neutral	D	0.60335987	None	None	N
D/C	0.5818	likely_pathogenic	0.5211	ambiguous	0.058	Stabilizing	0.998	D	0.623	neutral	None	None	None	None	N
D/E	0.1248	likely_benign	0.1185	benign	-0.194	Destabilizing	0.006	N	0.218	neutral	N	0.449867233	None	None	N
D/F	0.4895	ambiguous	0.4684	ambiguous	-0.241	Destabilizing	0.993	D	0.581	neutral	None	None	None	None	N
D/G	0.1436	likely_benign	0.1445	benign	-0.37	Destabilizing	0.822	D	0.365	neutral	D	0.546726818	None	None	N
D/H	0.2307	likely_benign	0.2138	benign	-0.095	Destabilizing	0.992	D	0.391	neutral	D	0.602515364	None	None	N
D/I	0.2692	likely_benign	0.2635	benign	0.239	Stabilizing	0.978	D	0.594	neutral	None	None	None	None	N
D/K	0.2899	likely_benign	0.2778	benign	0.17	Stabilizing	0.754	D	0.341	neutral	None	None	None	None	N
D/L	0.3608	ambiguous	0.3404	ambiguous	0.239	Stabilizing	0.956	D	0.6	neutral	None	None	None	None	N
D/M	0.5653	likely_pathogenic	0.5263	ambiguous	0.34	Stabilizing	0.998	D	0.611	neutral	None	None	None	None	N
D/N	0.0923	likely_benign	0.0923	benign	0.091	Stabilizing	0.822	D	0.36	neutral	D	0.540477443	None	None	N
D/P	0.817	likely_pathogenic	0.8058	pathogenic	0.118	Stabilizing	0.978	D	0.391	neutral	None	None	None	None	N
D/Q	0.2861	likely_benign	0.2607	benign	0.109	Stabilizing	0.915	D	0.329	neutral	None	None	None	None	N
D/R	0.3156	likely_benign	0.2998	benign	0.337	Stabilizing	0.956	D	0.518	neutral	None	None	None	None	N
D/S	0.1234	likely_benign	0.1172	benign	-0.074	Destabilizing	0.754	D	0.309	neutral	None	None	None	None	N
D/T	0.2058	likely_benign	0.2032	benign	0.056	Stabilizing	0.956	D	0.345	neutral	None	None	None	None	N
D/V	0.1438	likely_benign	0.141	benign	0.118	Stabilizing	0.942	D	0.601	neutral	D	0.541311267	None	None	N
D/W	0.7924	likely_pathogenic	0.7641	pathogenic	-0.176	Destabilizing	0.998	D	0.633	neutral	None	None	None	None	N
D/Y	0.1547	likely_benign	0.1549	benign	-0.03	Destabilizing	0.99	D	0.58	neutral	D	0.642138192	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.