TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27905	83938;83939;83940	chr2:178562419;178562418;178562417	chr2:179427146;179427145;179427144
N2AB	26264	79015;79016;79017	chr2:178562419;178562418;178562417	chr2:179427146;179427145;179427144
N2A	25337	76234;76235;76236	chr2:178562419;178562418;178562417	chr2:179427146;179427145;179427144
N2B	18840	56743;56744;56745	chr2:178562419;178562418;178562417	chr2:179427146;179427145;179427144
Novex-1	18965	57118;57119;57120	chr2:178562419;178562418;178562417	chr2:179427146;179427145;179427144
Novex-2	19032	57319;57320;57321	chr2:178562419;178562418;178562417	chr2:179427146;179427145;179427144
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: Fn3-91
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.4472
• 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/E	rs879057080	None	0.997	N	0.697	0.464	None	gnomAD-4.0.0	1.59339E-06	None	None	None	None	N	None	5.66765E-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	0.3507	ambiguous	0.415	ambiguous	0.044	Stabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	N
K/C	0.8262	likely_pathogenic	0.8581	pathogenic	-0.231	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
K/D	0.7544	likely_pathogenic	0.8081	pathogenic	0.017	Stabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
K/E	0.3015	likely_benign	0.366	ambiguous	0.008	Stabilizing	0.997	D	0.697	prob.neutral	N	0.488446683	None	None	N
K/F	0.8934	likely_pathogenic	0.9197	pathogenic	-0.254	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
K/G	0.5542	ambiguous	0.626	pathogenic	-0.122	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
K/H	0.4643	ambiguous	0.5248	ambiguous	-0.397	Destabilizing	1.0	D	0.629	neutral	None	None	None	None	N
K/I	0.464	ambiguous	0.5337	ambiguous	0.397	Stabilizing	0.992	D	0.723	prob.delet.	N	0.46844595	None	None	N
K/L	0.5073	ambiguous	0.5713	pathogenic	0.397	Stabilizing	0.994	D	0.679	prob.neutral	None	None	None	None	N
K/M	0.3796	ambiguous	0.4383	ambiguous	0.21	Stabilizing	1.0	D	0.624	neutral	None	None	None	None	N
K/N	0.6318	likely_pathogenic	0.6992	pathogenic	0.235	Stabilizing	1.0	D	0.707	prob.neutral	N	0.472333517	None	None	N
K/P	0.661	likely_pathogenic	0.717	pathogenic	0.306	Stabilizing	1.0	D	0.67	neutral	None	None	None	None	N
K/Q	0.2071	likely_benign	0.2383	benign	0.044	Stabilizing	0.998	D	0.693	prob.neutral	N	0.485789736	None	None	N
K/R	0.0832	likely_benign	0.0879	benign	-0.007	Destabilizing	0.996	D	0.613	neutral	N	0.480220329	None	None	N
K/S	0.5342	ambiguous	0.6017	pathogenic	-0.222	Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	N
K/T	0.2962	likely_benign	0.3589	ambiguous	-0.095	Destabilizing	0.999	D	0.681	prob.neutral	N	0.516364003	None	None	N
K/V	0.3853	ambiguous	0.446	ambiguous	0.306	Stabilizing	0.996	D	0.716	prob.delet.	None	None	None	None	N
K/W	0.8855	likely_pathogenic	0.9091	pathogenic	-0.289	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	N
K/Y	0.8035	likely_pathogenic	0.8436	pathogenic	0.08	Stabilizing	0.999	D	0.687	prob.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.