TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20513	61762;61763;61764	chr2:178590188;178590187;178590186	chr2:179454915;179454914;179454913
N2AB	18872	56839;56840;56841	chr2:178590188;178590187;178590186	chr2:179454915;179454914;179454913
N2A	17945	54058;54059;54060	chr2:178590188;178590187;178590186	chr2:179454915;179454914;179454913
N2B	11448	34567;34568;34569	chr2:178590188;178590187;178590186	chr2:179454915;179454914;179454913
Novex-1	11573	34942;34943;34944	chr2:178590188;178590187;178590186	chr2:179454915;179454914;179454913
Novex-2	11640	35143;35144;35145	chr2:178590188;178590187;178590186	chr2:179454915;179454914;179454913
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-121
• Domain position: 35
• Structural Position: 51
• Q(SASA): 0.7179
• 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
E/K	None	None	0.811	N	0.494	0.204	0.230578612272	gnomAD-4.0.0	2.40065E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	3.66327E-05

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
E/A	0.2067	likely_benign	0.2318	benign	-0.2	Destabilizing	0.811	D	0.503	neutral	N	0.474871592	None	None	I
E/C	0.8618	likely_pathogenic	0.8795	pathogenic	-0.004	Destabilizing	0.999	D	0.648	neutral	None	None	None	None	I
E/D	0.0679	likely_benign	0.0747	benign	-0.151	Destabilizing	0.011	N	0.198	neutral	N	0.365794326	None	None	I
E/F	0.8569	likely_pathogenic	0.8916	pathogenic	-0.069	Destabilizing	0.996	D	0.599	neutral	None	None	None	None	I
E/G	0.137	likely_benign	0.1618	benign	-0.373	Destabilizing	0.026	N	0.366	neutral	N	0.432848825	None	None	I
E/H	0.6737	likely_pathogenic	0.7198	pathogenic	0.253	Stabilizing	0.988	D	0.421	neutral	None	None	None	None	I
E/I	0.6924	likely_pathogenic	0.7507	pathogenic	0.215	Stabilizing	0.988	D	0.607	neutral	None	None	None	None	I
E/K	0.4305	ambiguous	0.5052	ambiguous	0.531	Stabilizing	0.811	D	0.494	neutral	N	0.482875	None	None	I
E/L	0.6086	likely_pathogenic	0.6574	pathogenic	0.215	Stabilizing	0.976	D	0.581	neutral	None	None	None	None	I
E/M	0.6898	likely_pathogenic	0.7237	pathogenic	0.197	Stabilizing	0.999	D	0.597	neutral	None	None	None	None	I
E/N	0.2112	likely_benign	0.2523	benign	0.155	Stabilizing	0.851	D	0.455	neutral	None	None	None	None	I
E/P	0.885	likely_pathogenic	0.8883	pathogenic	0.097	Stabilizing	0.988	D	0.514	neutral	None	None	None	None	I
E/Q	0.2695	likely_benign	0.2953	benign	0.209	Stabilizing	0.437	N	0.247	neutral	N	0.499017889	None	None	I
E/R	0.5402	ambiguous	0.5897	pathogenic	0.693	Stabilizing	0.976	D	0.425	neutral	None	None	None	None	I
E/S	0.2511	likely_benign	0.2914	benign	0.021	Stabilizing	0.919	D	0.457	neutral	None	None	None	None	I
E/T	0.4188	ambiguous	0.4844	ambiguous	0.175	Stabilizing	0.919	D	0.518	neutral	None	None	None	None	I
E/V	0.4692	ambiguous	0.524	ambiguous	0.097	Stabilizing	0.984	D	0.549	neutral	N	0.491726557	None	None	I
E/W	0.9436	likely_pathogenic	0.9528	pathogenic	0.062	Stabilizing	0.999	D	0.66	neutral	None	None	None	None	I
E/Y	0.6882	likely_pathogenic	0.7487	pathogenic	0.174	Stabilizing	0.996	D	0.589	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.