TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8619	26080;26081;26082	chr2:178715559;178715558;178715557	chr2:179580286;179580285;179580284
N2AB	8302	25129;25130;25131	chr2:178715559;178715558;178715557	chr2:179580286;179580285;179580284
N2A	7375	22348;22349;22350	chr2:178715559;178715558;178715557	chr2:179580286;179580285;179580284
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: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-71
• Domain position: 71
• Structural Position: 153
• Q(SASA): 0.3073
• 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/G	rs2077359221	None	0.95	N	0.512	0.361	0.341696514166	gnomAD-4.0.0	4.10566E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	3.47102E-04	3.59823E-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	0.2873	likely_benign	0.1881	benign	-0.446	Destabilizing	0.637	D	0.533	neutral	D	0.534750268	None	None	N
D/C	0.7429	likely_pathogenic	0.5908	pathogenic	0.049	Stabilizing	0.993	D	0.619	neutral	None	None	None	None	N
D/E	0.2664	likely_benign	0.2072	benign	-0.715	Destabilizing	0.747	D	0.5	neutral	N	0.45586541	None	None	N
D/F	0.5122	ambiguous	0.4032	ambiguous	-0.749	Destabilizing	0.993	D	0.632	neutral	None	None	None	None	N
D/G	0.3554	ambiguous	0.2363	benign	-0.683	Destabilizing	0.95	D	0.512	neutral	N	0.50217765	None	None	N
D/H	0.3448	ambiguous	0.2322	benign	-1.06	Destabilizing	0.998	D	0.561	neutral	D	0.531115317	None	None	N
D/I	0.3	likely_benign	0.2195	benign	0.145	Stabilizing	0.213	N	0.443	neutral	None	None	None	None	N
D/K	0.5143	ambiguous	0.3564	ambiguous	0.066	Stabilizing	0.998	D	0.547	neutral	None	None	None	None	N
D/L	0.415	ambiguous	0.3101	benign	0.145	Stabilizing	0.807	D	0.498	neutral	None	None	None	None	N
D/M	0.6068	likely_pathogenic	0.506	ambiguous	0.657	Stabilizing	0.982	D	0.622	neutral	None	None	None	None	N
D/N	0.1213	likely_benign	0.0902	benign	-0.221	Destabilizing	0.976	D	0.531	neutral	N	0.505467511	None	None	N
D/P	0.9019	likely_pathogenic	0.7958	pathogenic	-0.03	Destabilizing	0.896	D	0.589	neutral	None	None	None	None	N
D/Q	0.4616	ambiguous	0.3308	benign	-0.187	Destabilizing	0.994	D	0.561	neutral	None	None	None	None	N
D/R	0.5056	ambiguous	0.3545	ambiguous	-0.062	Destabilizing	0.998	D	0.621	neutral	None	None	None	None	N
D/S	0.1988	likely_benign	0.1351	benign	-0.372	Destabilizing	0.919	D	0.493	neutral	None	None	None	None	N
D/T	0.3233	likely_benign	0.2267	benign	-0.172	Destabilizing	0.715	D	0.477	neutral	None	None	None	None	N
D/V	0.2145	likely_benign	0.152	benign	-0.03	Destabilizing	0.015	N	0.398	neutral	N	0.440821387	None	None	N
D/W	0.8834	likely_pathogenic	0.8239	pathogenic	-0.73	Destabilizing	0.999	D	0.638	neutral	None	None	None	None	N
D/Y	0.1934	likely_benign	0.1439	benign	-0.528	Destabilizing	0.997	D	0.637	neutral	N	0.486301894	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.