TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2537	7834;7835;7836	chr2:178773355;178773354;178773353	chr2:179638082;179638081;179638080
N2AB	2537	7834;7835;7836	chr2:178773355;178773354;178773353	chr2:179638082;179638081;179638080
N2A	2537	7834;7835;7836	chr2:178773355;178773354;178773353	chr2:179638082;179638081;179638080
N2B	2491	7696;7697;7698	chr2:178773355;178773354;178773353	chr2:179638082;179638081;179638080
Novex-1	2491	7696;7697;7698	chr2:178773355;178773354;178773353	chr2:179638082;179638081;179638080
Novex-2	2491	7696;7697;7698	chr2:178773355;178773354;178773353	chr2:179638082;179638081;179638080
Novex-3	2537	7834;7835;7836	chr2:178773355;178773354;178773353	chr2:179638082;179638081;179638080

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-15
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.5485
• 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/S	None	None	0.379	N	0.452	0.359	0.28722502521	gnomAD-4.0.0	6.84136E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99319E-07	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	0.5082	ambiguous	0.4493	ambiguous	-0.441	Destabilizing	0.25	N	0.435	neutral	None	None	None	None	N
R/C	0.3034	likely_benign	0.2907	benign	-0.506	Destabilizing	0.992	D	0.532	neutral	None	None	None	None	N
R/D	0.6849	likely_pathogenic	0.6423	pathogenic	0.062	Stabilizing	0.617	D	0.493	neutral	None	None	None	None	N
R/E	0.3932	ambiguous	0.3574	ambiguous	0.183	Stabilizing	0.25	N	0.447	neutral	None	None	None	None	N
R/F	0.767	likely_pathogenic	0.7288	pathogenic	-0.301	Destabilizing	0.972	D	0.515	neutral	None	None	None	None	N
R/G	0.3345	likely_benign	0.2917	benign	-0.735	Destabilizing	0.549	D	0.471	neutral	N	0.501602709	None	None	N
R/H	0.1163	likely_benign	0.1186	benign	-1.049	Destabilizing	0.92	D	0.494	neutral	None	None	None	None	N
R/I	0.5193	ambiguous	0.4508	ambiguous	0.338	Stabilizing	0.896	D	0.519	neutral	N	0.505657197	None	None	N
R/K	0.1008	likely_benign	0.0983	benign	-0.477	Destabilizing	0.001	N	0.126	neutral	N	0.421657177	None	None	N
R/L	0.459	ambiguous	0.4173	ambiguous	0.338	Stabilizing	0.617	D	0.471	neutral	None	None	None	None	N
R/M	0.4827	ambiguous	0.4253	ambiguous	-0.142	Destabilizing	0.972	D	0.504	neutral	None	None	None	None	N
R/N	0.5332	ambiguous	0.4732	ambiguous	-0.105	Destabilizing	0.617	D	0.461	neutral	None	None	None	None	N
R/P	0.93	likely_pathogenic	0.915	pathogenic	0.1	Stabilizing	0.92	D	0.495	neutral	None	None	None	None	N
R/Q	0.1233	likely_benign	0.1239	benign	-0.204	Destabilizing	0.447	N	0.495	neutral	None	None	None	None	N
R/S	0.494	ambiguous	0.4372	ambiguous	-0.738	Destabilizing	0.379	N	0.452	neutral	N	0.510586158	None	None	N
R/T	0.2604	likely_benign	0.2231	benign	-0.439	Destabilizing	0.549	D	0.471	neutral	N	0.506793723	None	None	N
R/V	0.5757	likely_pathogenic	0.5267	ambiguous	0.1	Stabilizing	0.85	D	0.467	neutral	None	None	None	None	N
R/W	0.3093	likely_benign	0.2763	benign	-0.073	Destabilizing	0.992	D	0.596	neutral	None	None	None	None	N
R/Y	0.5752	likely_pathogenic	0.543	ambiguous	0.245	Stabilizing	0.972	D	0.531	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.