TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16493	49702;49703;49704	chr2:178613806;178613805;178613804	chr2:179478533;179478532;179478531
N2AB	14852	44779;44780;44781	chr2:178613806;178613805;178613804	chr2:179478533;179478532;179478531
N2A	13925	41998;41999;42000	chr2:178613806;178613805;178613804	chr2:179478533;179478532;179478531
N2B	7428	22507;22508;22509	chr2:178613806;178613805;178613804	chr2:179478533;179478532;179478531
Novex-1	7553	22882;22883;22884	chr2:178613806;178613805;178613804	chr2:179478533;179478532;179478531
Novex-2	7620	23083;23084;23085	chr2:178613806;178613805;178613804	chr2:179478533;179478532;179478531
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: Fn3-7
• Domain position: 44
• Structural Position: 54
• Q(SASA): 1.0571
• 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/H	None	None	0.931	N	0.519	0.327	0.402471007487	gnomAD-4.0.0	1.59363E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86338E-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	0.1581	likely_benign	0.1353	benign	-0.01	Destabilizing	0.201	N	0.452	neutral	N	0.472455412	None	None	N
D/C	0.632	likely_pathogenic	0.6079	pathogenic	0.092	Stabilizing	0.982	D	0.674	neutral	None	None	None	None	N
D/E	0.1044	likely_benign	0.0825	benign	-0.219	Destabilizing	0.001	N	0.351	neutral	N	0.434359957	None	None	N
D/F	0.6688	likely_pathogenic	0.6403	pathogenic	-0.223	Destabilizing	0.982	D	0.604	neutral	None	None	None	None	N
D/G	0.2048	likely_benign	0.1911	benign	-0.116	Destabilizing	0.334	N	0.468	neutral	N	0.42937787	None	None	N
D/H	0.3744	ambiguous	0.3659	ambiguous	0.239	Stabilizing	0.931	D	0.519	neutral	N	0.504753745	None	None	N
D/I	0.3054	likely_benign	0.2834	benign	0.196	Stabilizing	0.826	D	0.615	neutral	None	None	None	None	N
D/K	0.3892	ambiguous	0.3721	ambiguous	0.453	Stabilizing	0.25	N	0.463	neutral	None	None	None	None	N
D/L	0.3707	ambiguous	0.3176	benign	0.196	Stabilizing	0.7	D	0.597	neutral	None	None	None	None	N
D/M	0.5233	ambiguous	0.4566	ambiguous	0.159	Stabilizing	0.982	D	0.621	neutral	None	None	None	None	N
D/N	0.1149	likely_benign	0.1141	benign	0.392	Stabilizing	0.638	D	0.509	neutral	N	0.463750294	None	None	N
D/P	0.8673	likely_pathogenic	0.8182	pathogenic	0.146	Stabilizing	0.826	D	0.517	neutral	None	None	None	None	N
D/Q	0.317	likely_benign	0.2631	benign	0.367	Stabilizing	0.539	D	0.536	neutral	None	None	None	None	N
D/R	0.5302	ambiguous	0.5082	ambiguous	0.596	Stabilizing	0.539	D	0.519	neutral	None	None	None	None	N
D/S	0.1264	likely_benign	0.116	benign	0.257	Stabilizing	0.25	N	0.518	neutral	None	None	None	None	N
D/T	0.194	likely_benign	0.166	benign	0.334	Stabilizing	0.7	D	0.495	neutral	None	None	None	None	N
D/V	0.1831	likely_benign	0.1699	benign	0.146	Stabilizing	0.638	D	0.611	neutral	N	0.486463808	None	None	N
D/W	0.9288	likely_pathogenic	0.9108	pathogenic	-0.213	Destabilizing	0.982	D	0.685	prob.neutral	None	None	None	None	N
D/Y	0.3489	ambiguous	0.3565	ambiguous	-0.007	Destabilizing	0.976	D	0.604	neutral	N	0.472588048	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.