TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5127	15604;15605;15606	chr2:178734445;178734444;178734443	chr2:179599172;179599171;179599170
N2AB	4810	14653;14654;14655	chr2:178734445;178734444;178734443	chr2:179599172;179599171;179599170
N2A	3883	11872;11873;11874	chr2:178734445;178734444;178734443	chr2:179599172;179599171;179599170
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: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-34
• Domain position: 53
• Structural Position: 131
• Q(SASA): 0.7749
• 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	rs1349879607	0.326	0.801	N	0.242	0.21	0.176091768786	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	5.8E-05	None	0	0	None	0	None	0	0	0
K/N	rs1349879607	0.326	0.801	N	0.242	0.21	0.176091768786	gnomAD-4.0.0	1.3685E-06	None	None	None	None	N	None	0	4.47367E-05	None	0	0	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
K/A	0.2588	likely_benign	0.3309	benign	-0.011	Destabilizing	0.688	D	0.299	neutral	None	None	None	None	N
K/C	0.675	likely_pathogenic	0.7685	pathogenic	-0.486	Destabilizing	0.998	D	0.301	neutral	None	None	None	None	N
K/D	0.2458	likely_benign	0.3043	benign	-0.245	Destabilizing	0.016	N	0.159	neutral	None	None	None	None	N
K/E	0.1302	likely_benign	0.1612	benign	-0.263	Destabilizing	0.022	N	0.131	neutral	N	0.450974339	None	None	N
K/F	0.7032	likely_pathogenic	0.79	pathogenic	-0.387	Destabilizing	0.991	D	0.293	neutral	None	None	None	None	N
K/G	0.2356	likely_benign	0.2812	benign	-0.124	Destabilizing	0.915	D	0.325	neutral	None	None	None	None	N
K/H	0.2336	likely_benign	0.2764	benign	-0.235	Destabilizing	0.974	D	0.332	neutral	None	None	None	None	N
K/I	0.3986	ambiguous	0.5102	ambiguous	0.201	Stabilizing	0.974	D	0.32	neutral	None	None	None	None	N
K/L	0.3312	likely_benign	0.4191	ambiguous	0.201	Stabilizing	0.842	D	0.325	neutral	None	None	None	None	N
K/M	0.2383	likely_benign	0.3067	benign	-0.101	Destabilizing	0.989	D	0.329	neutral	N	0.500378658	None	None	N
K/N	0.1824	likely_benign	0.2225	benign	-0.029	Destabilizing	0.801	D	0.242	neutral	N	0.393694513	None	None	N
K/P	0.3903	ambiguous	0.4617	ambiguous	0.153	Stabilizing	0.991	D	0.368	neutral	None	None	None	None	N
K/Q	0.1113	likely_benign	0.1319	benign	-0.169	Destabilizing	0.136	N	0.164	neutral	N	0.440477909	None	None	N
K/R	0.0873	likely_benign	0.0898	benign	-0.138	Destabilizing	0.012	N	0.157	neutral	N	0.456920552	None	None	N
K/S	0.2426	likely_benign	0.3049	benign	-0.401	Destabilizing	0.688	D	0.223	neutral	None	None	None	None	N
K/T	0.1525	likely_benign	0.2084	benign	-0.306	Destabilizing	0.891	D	0.306	neutral	N	0.494511883	None	None	N
K/V	0.3558	ambiguous	0.4597	ambiguous	0.153	Stabilizing	0.915	D	0.329	neutral	None	None	None	None	N
K/W	0.7126	likely_pathogenic	0.7902	pathogenic	-0.49	Destabilizing	0.998	D	0.363	neutral	None	None	None	None	N
K/Y	0.4827	ambiguous	0.5754	pathogenic	-0.135	Destabilizing	0.991	D	0.31	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.