TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19881	59866;59867;59868	chr2:178592263;178592262;178592261	chr2:179456990;179456989;179456988
N2AB	18240	54943;54944;54945	chr2:178592263;178592262;178592261	chr2:179456990;179456989;179456988
N2A	17313	52162;52163;52164	chr2:178592263;178592262;178592261	chr2:179456990;179456989;179456988
N2B	10816	32671;32672;32673	chr2:178592263;178592262;178592261	chr2:179456990;179456989;179456988
Novex-1	10941	33046;33047;33048	chr2:178592263;178592262;178592261	chr2:179456990;179456989;179456988
Novex-2	11008	33247;33248;33249	chr2:178592263;178592262;178592261	chr2:179456990;179456989;179456988
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-32
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.1127
• 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
P/H	rs749276384	-2.69	0.999	D	0.866	0.616	0.725244559022	gnomAD-2.1.1	4.1E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.32E-05	None	0	0	0
P/H	rs749276384	-2.69	0.999	D	0.866	0.616	0.725244559022	gnomAD-4.0.0	6.85353E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.16602E-05	0
P/R	None	None	0.996	D	0.857	0.621	0.72322085207	gnomAD-4.0.0	1.37071E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80028E-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
P/A	0.5271	ambiguous	0.5462	ambiguous	-2.342	Highly Destabilizing	0.826	D	0.767	deleterious	D	0.574224889	None	None	N
P/C	0.7615	likely_pathogenic	0.8144	pathogenic	-1.871	Destabilizing	0.999	D	0.88	deleterious	None	None	None	None	N
P/D	0.9991	likely_pathogenic	0.9993	pathogenic	-3.358	Highly Destabilizing	0.997	D	0.829	deleterious	None	None	None	None	N
P/E	0.9957	likely_pathogenic	0.9968	pathogenic	-3.079	Highly Destabilizing	0.997	D	0.841	deleterious	None	None	None	None	N
P/F	0.9957	likely_pathogenic	0.9963	pathogenic	-1.182	Destabilizing	0.991	D	0.874	deleterious	None	None	None	None	N
P/G	0.9842	likely_pathogenic	0.9867	pathogenic	-2.891	Highly Destabilizing	0.99	D	0.844	deleterious	None	None	None	None	N
P/H	0.9954	likely_pathogenic	0.9963	pathogenic	-2.727	Highly Destabilizing	0.999	D	0.866	deleterious	D	0.6326393	None	None	N
P/I	0.5318	ambiguous	0.5839	pathogenic	-0.752	Destabilizing	0.079	N	0.667	neutral	None	None	None	None	N
P/K	0.9978	likely_pathogenic	0.9983	pathogenic	-1.93	Destabilizing	0.997	D	0.838	deleterious	None	None	None	None	N
P/L	0.6846	likely_pathogenic	0.714	pathogenic	-0.752	Destabilizing	0.704	D	0.806	deleterious	D	0.599964805	None	None	N
P/M	0.9247	likely_pathogenic	0.9373	pathogenic	-1.047	Destabilizing	0.991	D	0.868	deleterious	None	None	None	None	N
P/N	0.9967	likely_pathogenic	0.9977	pathogenic	-2.473	Highly Destabilizing	0.997	D	0.855	deleterious	None	None	None	None	N
P/Q	0.9898	likely_pathogenic	0.9921	pathogenic	-2.185	Highly Destabilizing	0.997	D	0.812	deleterious	None	None	None	None	N
P/R	0.9931	likely_pathogenic	0.9946	pathogenic	-1.897	Destabilizing	0.996	D	0.857	deleterious	D	0.632437496	None	None	N
P/S	0.9464	likely_pathogenic	0.9557	pathogenic	-2.964	Highly Destabilizing	0.959	D	0.827	deleterious	D	0.599964805	None	None	N
P/T	0.8092	likely_pathogenic	0.8325	pathogenic	-2.553	Highly Destabilizing	0.92	D	0.786	deleterious	D	0.590880023	None	None	N
P/V	0.2826	likely_benign	0.3105	benign	-1.264	Destabilizing	0.17	N	0.641	neutral	None	None	None	None	N
P/W	0.9994	likely_pathogenic	0.9995	pathogenic	-1.805	Destabilizing	0.999	D	0.871	deleterious	None	None	None	None	N
P/Y	0.9985	likely_pathogenic	0.9988	pathogenic	-1.505	Destabilizing	0.997	D	0.876	deleterious	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.