TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18318	55177;55178;55179	chr2:178602450;178602449;178602448	chr2:179467177;179467176;179467175
N2AB	16677	50254;50255;50256	chr2:178602450;178602449;178602448	chr2:179467177;179467176;179467175
N2A	15750	47473;47474;47475	chr2:178602450;178602449;178602448	chr2:179467177;179467176;179467175
N2B	9253	27982;27983;27984	chr2:178602450;178602449;178602448	chr2:179467177;179467176;179467175
Novex-1	9378	28357;28358;28359	chr2:178602450;178602449;178602448	chr2:179467177;179467176;179467175
Novex-2	9445	28558;28559;28560	chr2:178602450;178602449;178602448	chr2:179467177;179467176;179467175
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: Fn3-21
• Domain position: 47
• Structural Position: 64
• Q(SASA): 0.5577
• 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	rs951863461	None	0.37	N	0.358	0.061	0.159798565429	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
D/E	rs951863461	None	0.37	N	0.358	0.061	0.159798565429	gnomAD-4.0.0	2.5666E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.79294E-06	0	0
D/Y	None	None	1.0	N	0.615	0.462	0.686914373969	gnomAD-4.0.0	1.5942E-06	None	None	None	None	N	None	0	0	None	0	2.7908E-05	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
D/A	0.1078	likely_benign	0.1023	benign	-0.332	Destabilizing	0.978	D	0.507	neutral	N	0.504936288	None	None	N
D/C	0.4436	ambiguous	0.4671	ambiguous	-0.064	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
D/E	0.1039	likely_benign	0.0877	benign	-0.286	Destabilizing	0.37	N	0.358	neutral	N	0.41800795	None	None	N
D/F	0.4093	ambiguous	0.4447	ambiguous	-0.249	Destabilizing	1.0	D	0.612	neutral	None	None	None	None	N
D/G	0.1235	likely_benign	0.1304	benign	-0.528	Destabilizing	0.121	N	0.397	neutral	N	0.481269995	None	None	N
D/H	0.2233	likely_benign	0.2312	benign	-0.052	Destabilizing	1.0	D	0.481	neutral	N	0.513345128	None	None	N
D/I	0.2131	likely_benign	0.2038	benign	0.138	Stabilizing	0.999	D	0.626	neutral	None	None	None	None	N
D/K	0.2569	likely_benign	0.2576	benign	0.166	Stabilizing	0.995	D	0.456	neutral	None	None	None	None	N
D/L	0.2361	likely_benign	0.2423	benign	0.138	Stabilizing	0.998	D	0.636	neutral	None	None	None	None	N
D/M	0.4271	ambiguous	0.4194	ambiguous	0.24	Stabilizing	1.0	D	0.641	neutral	None	None	None	None	N
D/N	0.0932	likely_benign	0.0985	benign	-0.069	Destabilizing	0.997	D	0.45	neutral	N	0.495778087	None	None	N
D/P	0.632	likely_pathogenic	0.6824	pathogenic	0.003	Stabilizing	0.999	D	0.475	neutral	None	None	None	None	N
D/Q	0.218	likely_benign	0.2036	benign	-0.037	Destabilizing	0.995	D	0.477	neutral	None	None	None	None	N
D/R	0.293	likely_benign	0.3113	benign	0.383	Stabilizing	0.995	D	0.557	neutral	None	None	None	None	N
D/S	0.099	likely_benign	0.1016	benign	-0.207	Destabilizing	0.983	D	0.455	neutral	None	None	None	None	N
D/T	0.1533	likely_benign	0.1406	benign	-0.056	Destabilizing	0.998	D	0.484	neutral	None	None	None	None	N
D/V	0.1273	likely_benign	0.1238	benign	0.003	Stabilizing	0.997	D	0.645	neutral	N	0.492335137	None	None	N
D/W	0.773	likely_pathogenic	0.8006	pathogenic	-0.112	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	N
D/Y	0.1803	likely_benign	0.2088	benign	-0.016	Destabilizing	1.0	D	0.615	neutral	N	0.475803011	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.