TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2343	7252;7253;7254	chr2:178774237;178774236;178774235	chr2:179638964;179638963;179638962
N2AB	2343	7252;7253;7254	chr2:178774237;178774236;178774235	chr2:179638964;179638963;179638962
N2A	2343	7252;7253;7254	chr2:178774237;178774236;178774235	chr2:179638964;179638963;179638962
N2B	2297	7114;7115;7116	chr2:178774237;178774236;178774235	chr2:179638964;179638963;179638962
Novex-1	2297	7114;7115;7116	chr2:178774237;178774236;178774235	chr2:179638964;179638963;179638962
Novex-2	2297	7114;7115;7116	chr2:178774237;178774236;178774235	chr2:179638964;179638963;179638962
Novex-3	2343	7252;7253;7254	chr2:178774237;178774236;178774235	chr2:179638964;179638963;179638962

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-12
• Domain position: 77
• Structural Position: 166
• Q(SASA): 0.6208
• 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/Q	None	None	0.998	N	0.481	0.321	0.267755039894	gnomAD-4.0.0	6.84092E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99313E-07	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	0.4511	ambiguous	0.4403	ambiguous	-0.394	Destabilizing	0.985	D	0.573	neutral	None	None	None	None	N
K/C	0.6797	likely_pathogenic	0.6778	pathogenic	-0.556	Destabilizing	1.0	D	0.675	neutral	None	None	None	None	N
K/D	0.6169	likely_pathogenic	0.6016	pathogenic	0.156	Stabilizing	0.999	D	0.503	neutral	None	None	None	None	N
K/E	0.159	likely_benign	0.1542	benign	0.271	Stabilizing	0.993	D	0.507	neutral	N	0.502661404	None	None	N
K/F	0.6899	likely_pathogenic	0.6848	pathogenic	-0.205	Destabilizing	0.991	D	0.665	neutral	None	None	None	None	N
K/G	0.5718	likely_pathogenic	0.5643	pathogenic	-0.716	Destabilizing	0.995	D	0.527	neutral	None	None	None	None	N
K/H	0.3002	likely_benign	0.2964	benign	-0.875	Destabilizing	1.0	D	0.546	neutral	None	None	None	None	N
K/I	0.2593	likely_benign	0.2545	benign	0.425	Stabilizing	0.925	D	0.591	neutral	N	0.516435349	None	None	N
K/L	0.299	likely_benign	0.3	benign	0.425	Stabilizing	0.041	N	0.3	neutral	None	None	None	None	N
K/M	0.2099	likely_benign	0.2069	benign	0.008	Stabilizing	0.991	D	0.542	neutral	None	None	None	None	N
K/N	0.3667	ambiguous	0.3606	ambiguous	-0.303	Destabilizing	0.998	D	0.44	neutral	N	0.509714701	None	None	N
K/P	0.9659	likely_pathogenic	0.9607	pathogenic	0.181	Stabilizing	0.999	D	0.535	neutral	None	None	None	None	N
K/Q	0.1114	likely_benign	0.1081	benign	-0.267	Destabilizing	0.998	D	0.481	neutral	N	0.482668964	None	None	N
K/R	0.089	likely_benign	0.0873	benign	-0.299	Destabilizing	0.993	D	0.469	neutral	N	0.487015734	None	None	N
K/S	0.4361	ambiguous	0.4292	ambiguous	-0.891	Destabilizing	0.995	D	0.465	neutral	None	None	None	None	N
K/T	0.234	likely_benign	0.2299	benign	-0.57	Destabilizing	0.98	D	0.551	neutral	N	0.514729518	None	None	N
K/V	0.2865	likely_benign	0.2816	benign	0.181	Stabilizing	0.942	D	0.578	neutral	None	None	None	None	N
K/W	0.7435	likely_pathogenic	0.7358	pathogenic	-0.172	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
K/Y	0.5528	ambiguous	0.5466	ambiguous	0.146	Stabilizing	0.999	D	0.632	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.