TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17413	52462;52463;52464	chr2:178608774;178608773;178608772	chr2:179473501;179473500;179473499
N2AB	15772	47539;47540;47541	chr2:178608774;178608773;178608772	chr2:179473501;179473500;179473499
N2A	14845	44758;44759;44760	chr2:178608774;178608773;178608772	chr2:179473501;179473500;179473499
N2B	8348	25267;25268;25269	chr2:178608774;178608773;178608772	chr2:179473501;179473500;179473499
Novex-1	8473	25642;25643;25644	chr2:178608774;178608773;178608772	chr2:179473501;179473500;179473499
Novex-2	8540	25843;25844;25845	chr2:178608774;178608773;178608772	chr2:179473501;179473500;179473499
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-14
• Domain position: 45
• Structural Position: 60
• Q(SASA): 0.4025
• 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
K/N	rs749984408	-0.511	0.999	N	0.577	0.219	0.20962295	gnomAD-4.0.0	3.18786E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88608E-05	0	2.86226E-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
K/A	0.498	ambiguous	0.3985	ambiguous	-0.073	Destabilizing	0.998	D	0.425	neutral	None	None	None	None	N
K/C	0.8067	likely_pathogenic	0.7309	pathogenic	-0.068	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
K/D	0.729	likely_pathogenic	0.6659	pathogenic	0.019	Stabilizing	1.0	D	0.609	neutral	None	None	None	None	N
K/E	0.3951	ambiguous	0.3213	benign	0.018	Stabilizing	0.996	D	0.371	neutral	N	0.49252436	None	None	N
K/F	0.8812	likely_pathogenic	0.8139	pathogenic	-0.335	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
K/G	0.6631	likely_pathogenic	0.557	ambiguous	-0.283	Destabilizing	1.0	D	0.54	neutral	None	None	None	None	N
K/H	0.3901	ambiguous	0.3348	benign	-0.723	Destabilizing	1.0	D	0.644	neutral	None	None	None	None	N
K/I	0.4751	ambiguous	0.3894	ambiguous	0.404	Stabilizing	1.0	D	0.729	prob.delet.	D	0.52348477	None	None	N
K/L	0.4719	ambiguous	0.3881	ambiguous	0.404	Stabilizing	1.0	D	0.54	neutral	None	None	None	None	N
K/M	0.4083	ambiguous	0.3274	benign	0.427	Stabilizing	1.0	D	0.651	neutral	None	None	None	None	N
K/N	0.5747	likely_pathogenic	0.5027	ambiguous	0.291	Stabilizing	0.999	D	0.577	neutral	N	0.49408457	None	None	N
K/P	0.9188	likely_pathogenic	0.865	pathogenic	0.273	Stabilizing	1.0	D	0.598	neutral	None	None	None	None	N
K/Q	0.2098	likely_benign	0.1754	benign	0.045	Stabilizing	0.999	D	0.566	neutral	N	0.49981847	None	None	N
K/R	0.0951	likely_benign	0.086	benign	-0.035	Destabilizing	0.64	D	0.225	neutral	N	0.4362498	None	None	N
K/S	0.5722	likely_pathogenic	0.4857	ambiguous	-0.225	Destabilizing	0.998	D	0.451	neutral	None	None	None	None	N
K/T	0.3595	ambiguous	0.2829	benign	-0.077	Destabilizing	0.999	D	0.571	neutral	N	0.45092845	None	None	N
K/V	0.4441	ambiguous	0.3594	ambiguous	0.273	Stabilizing	1.0	D	0.615	neutral	None	None	None	None	N
K/W	0.8889	likely_pathogenic	0.824	pathogenic	-0.31	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
K/Y	0.7608	likely_pathogenic	0.6824	pathogenic	0.055	Stabilizing	1.0	D	0.68	prob.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.