TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25632	77119;77120;77121	chr2:178569238;178569237;178569236	chr2:179433965;179433964;179433963
N2AB	23991	72196;72197;72198	chr2:178569238;178569237;178569236	chr2:179433965;179433964;179433963
N2A	23064	69415;69416;69417	chr2:178569238;178569237;178569236	chr2:179433965;179433964;179433963
N2B	16567	49924;49925;49926	chr2:178569238;178569237;178569236	chr2:179433965;179433964;179433963
Novex-1	16692	50299;50300;50301	chr2:178569238;178569237;178569236	chr2:179433965;179433964;179433963
Novex-2	16759	50500;50501;50502	chr2:178569238;178569237;178569236	chr2:179433965;179433964;179433963
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-74
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.7728
• 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	rs984799615	None	0.924	N	0.582	0.397	0.44349138644	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	4.82E-05	0	0	0	0	None	0	0	0	0	0
K/T	rs984799615	None	0.924	N	0.582	0.397	0.44349138644	gnomAD-4.0.0	4.05989E-06	None	None	None	None	I	None	6.98763E-05	0	None	0	0	None	0	0	0	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	0.594	likely_pathogenic	0.6429	pathogenic	-0.048	Destabilizing	0.939	D	0.555	neutral	None	None	None	None	I
K/C	0.8508	likely_pathogenic	0.8843	pathogenic	-0.193	Destabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	I
K/D	0.8552	likely_pathogenic	0.8784	pathogenic	0.095	Stabilizing	0.885	D	0.553	neutral	None	None	None	None	I
K/E	0.5027	ambiguous	0.5427	ambiguous	0.121	Stabilizing	0.011	N	0.331	neutral	N	0.459334498	None	None	I
K/F	0.9299	likely_pathogenic	0.9458	pathogenic	-0.127	Destabilizing	0.998	D	0.633	neutral	None	None	None	None	I
K/G	0.7643	likely_pathogenic	0.8122	pathogenic	-0.286	Destabilizing	0.982	D	0.532	neutral	None	None	None	None	I
K/H	0.4968	ambiguous	0.5579	ambiguous	-0.555	Destabilizing	0.994	D	0.618	neutral	None	None	None	None	I
K/I	0.6189	likely_pathogenic	0.651	pathogenic	0.51	Stabilizing	0.708	D	0.651	neutral	N	0.519020306	None	None	I
K/L	0.6329	likely_pathogenic	0.6781	pathogenic	0.51	Stabilizing	0.613	D	0.55	neutral	None	None	None	None	I
K/M	0.5478	ambiguous	0.5947	pathogenic	0.278	Stabilizing	0.993	D	0.611	neutral	None	None	None	None	I
K/N	0.758	likely_pathogenic	0.7887	pathogenic	0.188	Stabilizing	0.976	D	0.626	neutral	N	0.515267925	None	None	I
K/P	0.6488	likely_pathogenic	0.6869	pathogenic	0.353	Stabilizing	0.991	D	0.634	neutral	None	None	None	None	I
K/Q	0.2762	likely_benign	0.3176	benign	0.028	Stabilizing	0.711	D	0.615	neutral	N	0.519769668	None	None	I
K/R	0.0796	likely_benign	0.0852	benign	-0.093	Destabilizing	0.682	D	0.491	neutral	N	0.483022221	None	None	I
K/S	0.7439	likely_pathogenic	0.7827	pathogenic	-0.331	Destabilizing	0.939	D	0.549	neutral	None	None	None	None	I
K/T	0.4756	ambiguous	0.5139	ambiguous	-0.145	Destabilizing	0.924	D	0.582	neutral	N	0.467494444	None	None	I
K/V	0.5287	ambiguous	0.5667	pathogenic	0.353	Stabilizing	0.809	D	0.632	neutral	None	None	None	None	I
K/W	0.91	likely_pathogenic	0.9347	pathogenic	-0.107	Destabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	I
K/Y	0.8469	likely_pathogenic	0.8773	pathogenic	0.225	Stabilizing	0.939	D	0.645	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.