TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32509	97750;97751;97752	chr2:178541552;178541551;178541550	chr2:179406279;179406278;179406277
N2AB	30868	92827;92828;92829	chr2:178541552;178541551;178541550	chr2:179406279;179406278;179406277
N2A	29941	90046;90047;90048	chr2:178541552;178541551;178541550	chr2:179406279;179406278;179406277
N2B	23444	70555;70556;70557	chr2:178541552;178541551;178541550	chr2:179406279;179406278;179406277
Novex-1	23569	70930;70931;70932	chr2:178541552;178541551;178541550	chr2:179406279;179406278;179406277
Novex-2	23636	71131;71132;71133	chr2:178541552;178541551;178541550	chr2:179406279;179406278;179406277
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Fn3-125
• Domain position: 11
• Structural Position: 13
• Q(SASA): 0.6604
• Predicted PPI site: I

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
F/L	None	None	None	N	0.129	0.244	0.225902525712	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
F/V	rs1233350994	-0.632	0.09	N	0.415	0.251	0.464183351471	gnomAD-2.1.1	4.07E-06	None	None	None	None	I	None	0	0	None	0	5.65E-05	None	0	None	0	0	0
F/V	rs1233350994	-0.632	0.09	N	0.415	0.251	0.464183351471	gnomAD-4.0.0	9.60257E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.05E-05	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
F/A	0.28	likely_benign	0.2324	benign	-1.465	Destabilizing	0.388	N	0.461	neutral	None	None	None	None	I
F/C	0.2467	likely_benign	0.2032	benign	-0.392	Destabilizing	0.975	D	0.457	neutral	N	0.429649096	None	None	I
F/D	0.5918	likely_pathogenic	0.5737	pathogenic	0.147	Stabilizing	0.932	D	0.473	neutral	None	None	None	None	I
F/E	0.6115	likely_pathogenic	0.5974	pathogenic	0.14	Stabilizing	0.818	D	0.473	neutral	None	None	None	None	I
F/G	0.5495	ambiguous	0.4868	ambiguous	-1.708	Destabilizing	0.818	D	0.433	neutral	None	None	None	None	I
F/H	0.3717	ambiguous	0.3508	ambiguous	-0.146	Destabilizing	0.981	D	0.42	neutral	None	None	None	None	I
F/I	0.1646	likely_benign	0.1463	benign	-0.804	Destabilizing	0.09	N	0.422	neutral	N	0.417487875	None	None	I
F/K	0.6849	likely_pathogenic	0.6708	pathogenic	-0.423	Destabilizing	0.818	D	0.443	neutral	None	None	None	None	I
F/L	0.6718	likely_pathogenic	0.5739	pathogenic	-0.804	Destabilizing	None	N	0.129	neutral	N	0.373043665	None	None	I
F/M	0.3549	ambiguous	0.3026	benign	-0.5	Destabilizing	0.69	D	0.446	neutral	None	None	None	None	I
F/N	0.4473	ambiguous	0.4076	ambiguous	-0.305	Destabilizing	0.932	D	0.465	neutral	None	None	None	None	I
F/P	0.9601	likely_pathogenic	0.9432	pathogenic	-1.008	Destabilizing	0.932	D	0.459	neutral	None	None	None	None	I
F/Q	0.5483	ambiguous	0.5081	ambiguous	-0.443	Destabilizing	0.932	D	0.46	neutral	None	None	None	None	I
F/R	0.533	ambiguous	0.5125	ambiguous	0.213	Stabilizing	0.818	D	0.469	neutral	None	None	None	None	I
F/S	0.1735	likely_benign	0.1533	benign	-1.021	Destabilizing	0.492	N	0.447	neutral	N	0.323497492	None	None	I
F/T	0.183	likely_benign	0.1615	benign	-0.939	Destabilizing	0.388	N	0.451	neutral	None	None	None	None	I
F/V	0.1574	likely_benign	0.138	benign	-1.008	Destabilizing	0.09	N	0.415	neutral	N	0.379238918	None	None	I
F/W	0.3725	ambiguous	0.3501	ambiguous	-0.448	Destabilizing	0.981	D	0.432	neutral	None	None	None	None	I
F/Y	0.1494	likely_benign	0.1444	benign	-0.485	Destabilizing	0.492	N	0.436	neutral	N	0.44051945	None	None	I

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.