TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28027	84304;84305;84306	chr2:178562053;178562052;178562051	chr2:179426780;179426779;179426778
N2AB	26386	79381;79382;79383	chr2:178562053;178562052;178562051	chr2:179426780;179426779;179426778
N2A	25459	76600;76601;76602	chr2:178562053;178562052;178562051	chr2:179426780;179426779;179426778
N2B	18962	57109;57110;57111	chr2:178562053;178562052;178562051	chr2:179426780;179426779;179426778
Novex-1	19087	57484;57485;57486	chr2:178562053;178562052;178562051	chr2:179426780;179426779;179426778
Novex-2	19154	57685;57686;57687	chr2:178562053;178562052;178562051	chr2:179426780;179426779;179426778
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-142
• Domain position: 65
• Structural Position: 146
• Q(SASA): 0.6596
• 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/E	rs1647599149	None	0.027	N	0.278	0.087	0.220303561663	gnomAD-4.0.0	3.60101E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.93756E-06	0	0
K/N	None	None	None	N	0.247	0.212	0.136095386433	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31252E-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	0.2697	likely_benign	0.2578	benign	0.038	Stabilizing	0.067	N	0.308	neutral	None	None	None	None	N
K/C	0.5349	ambiguous	0.5301	ambiguous	-0.4	Destabilizing	0.935	D	0.299	neutral	None	None	None	None	N
K/D	0.6218	likely_pathogenic	0.6252	pathogenic	-0.168	Destabilizing	0.081	N	0.308	neutral	None	None	None	None	N
K/E	0.1679	likely_benign	0.1694	benign	-0.17	Destabilizing	0.027	N	0.278	neutral	N	0.495553509	None	None	N
K/F	0.7044	likely_pathogenic	0.6741	pathogenic	-0.25	Destabilizing	0.555	D	0.295	neutral	None	None	None	None	N
K/G	0.3476	ambiguous	0.3441	ambiguous	-0.114	Destabilizing	0.081	N	0.317	neutral	None	None	None	None	N
K/H	0.3003	likely_benign	0.2951	benign	-0.227	Destabilizing	0.001	N	0.232	neutral	None	None	None	None	N
K/I	0.2602	likely_benign	0.2425	benign	0.358	Stabilizing	0.555	D	0.313	neutral	None	None	None	None	N
K/L	0.2859	likely_benign	0.2676	benign	0.358	Stabilizing	0.149	N	0.322	neutral	None	None	None	None	N
K/M	0.2242	likely_benign	0.2127	benign	-0.028	Destabilizing	0.915	D	0.309	neutral	N	0.460794222	None	None	N
K/N	0.5013	ambiguous	0.4867	ambiguous	0.046	Stabilizing	None	N	0.247	neutral	N	0.472822091	None	None	N
K/P	0.4982	ambiguous	0.4403	ambiguous	0.277	Stabilizing	0.555	D	0.315	neutral	None	None	None	None	N
K/Q	0.1205	likely_benign	0.1198	benign	-0.085	Destabilizing	0.062	N	0.281	neutral	N	0.460705317	None	None	N
K/R	0.0575	likely_benign	0.0577	benign	-0.069	Destabilizing	None	N	0.165	neutral	N	0.388828689	None	None	N
K/S	0.398	ambiguous	0.3795	ambiguous	-0.343	Destabilizing	0.081	N	0.242	neutral	None	None	None	None	N
K/T	0.1969	likely_benign	0.1922	benign	-0.216	Destabilizing	0.117	N	0.291	neutral	N	0.456412903	None	None	N
K/V	0.2531	likely_benign	0.2364	benign	0.277	Stabilizing	0.38	N	0.312	neutral	None	None	None	None	N
K/W	0.5667	likely_pathogenic	0.5641	pathogenic	-0.341	Destabilizing	0.935	D	0.395	neutral	None	None	None	None	N
K/Y	0.5593	ambiguous	0.5416	ambiguous	0.016	Stabilizing	0.38	N	0.322	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.