TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28730	86413;86414;86415	chr2:178559944;178559943;178559942	chr2:179424671;179424670;179424669
N2AB	27089	81490;81491;81492	chr2:178559944;178559943;178559942	chr2:179424671;179424670;179424669
N2A	26162	78709;78710;78711	chr2:178559944;178559943;178559942	chr2:179424671;179424670;179424669
N2B	19665	59218;59219;59220	chr2:178559944;178559943;178559942	chr2:179424671;179424670;179424669
Novex-1	19790	59593;59594;59595	chr2:178559944;178559943;178559942	chr2:179424671;179424670;179424669
Novex-2	19857	59794;59795;59796	chr2:178559944;178559943;178559942	chr2:179424671;179424670;179424669
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: Fn3-97
• Domain position: 80
• Structural Position: 113
• Q(SASA): 0.5739
• 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
K/T	rs774912635	-0.011	0.988	N	0.558	0.473	0.393471546983	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
K/T	rs774912635	-0.011	0.988	N	0.558	0.473	0.393471546983	gnomAD-4.0.0	1.59132E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85819E-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	0.2987	likely_benign	0.2911	benign	0.046	Stabilizing	0.968	D	0.537	neutral	None	None	None	None	I
K/C	0.6542	likely_pathogenic	0.6741	pathogenic	-0.237	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	I
K/D	0.5906	likely_pathogenic	0.6094	pathogenic	-0.069	Destabilizing	0.991	D	0.558	neutral	None	None	None	None	I
K/E	0.2065	likely_benign	0.2107	benign	-0.071	Destabilizing	0.919	D	0.44	neutral	N	0.451197804	None	None	I
K/F	0.8105	likely_pathogenic	0.8177	pathogenic	-0.215	Destabilizing	1.0	D	0.641	neutral	None	None	None	None	I
K/G	0.4678	ambiguous	0.4994	ambiguous	-0.132	Destabilizing	0.991	D	0.499	neutral	None	None	None	None	I
K/H	0.3321	likely_benign	0.3434	ambiguous	-0.37	Destabilizing	0.999	D	0.596	neutral	None	None	None	None	I
K/I	0.3316	likely_benign	0.3136	benign	0.431	Stabilizing	0.995	D	0.653	neutral	None	None	None	None	I
K/L	0.378	ambiguous	0.3609	ambiguous	0.431	Stabilizing	0.991	D	0.499	neutral	None	None	None	None	I
K/M	0.248	likely_benign	0.2356	benign	0.184	Stabilizing	0.998	D	0.599	neutral	N	0.512459693	None	None	I
K/N	0.4719	ambiguous	0.4948	ambiguous	0.187	Stabilizing	0.988	D	0.596	neutral	D	0.524271411	None	None	I
K/P	0.7034	likely_pathogenic	0.7503	pathogenic	0.33	Stabilizing	0.995	D	0.605	neutral	None	None	None	None	I
K/Q	0.1409	likely_benign	0.1408	benign	0.015	Stabilizing	0.414	N	0.344	neutral	N	0.49167899	None	None	I
K/R	0.076	likely_benign	0.0757	benign	-0.032	Destabilizing	0.919	D	0.437	neutral	N	0.489158759	None	None	I
K/S	0.3945	ambiguous	0.4006	ambiguous	-0.249	Destabilizing	0.968	D	0.535	neutral	None	None	None	None	I
K/T	0.1735	likely_benign	0.1714	benign	-0.112	Destabilizing	0.988	D	0.558	neutral	N	0.505165575	None	None	I
K/V	0.2932	likely_benign	0.2838	benign	0.33	Stabilizing	0.991	D	0.587	neutral	None	None	None	None	I
K/W	0.7947	likely_pathogenic	0.8198	pathogenic	-0.262	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
K/Y	0.6873	likely_pathogenic	0.6897	pathogenic	0.099	Stabilizing	0.998	D	0.636	neutral	None	None	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.