TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24202	72829;72830;72831	chr2:178573528;178573527;178573526	chr2:179438255;179438254;179438253
N2AB	22561	67906;67907;67908	chr2:178573528;178573527;178573526	chr2:179438255;179438254;179438253
N2A	21634	65125;65126;65127	chr2:178573528;178573527;178573526	chr2:179438255;179438254;179438253
N2B	15137	45634;45635;45636	chr2:178573528;178573527;178573526	chr2:179438255;179438254;179438253
Novex-1	15262	46009;46010;46011	chr2:178573528;178573527;178573526	chr2:179438255;179438254;179438253
Novex-2	15329	46210;46211;46212	chr2:178573528;178573527;178573526	chr2:179438255;179438254;179438253
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: Fn3-63
• Domain position: 81
• Structural Position: 113
• Q(SASA): 0.6941
• 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/T	None	None	1.0	N	0.629	0.517	0.355034743287	gnomAD-4.0.0	2.22943E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.44928E-07	3.12588E-05	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	0.5155	ambiguous	0.616	pathogenic	-0.14	Destabilizing	0.999	D	0.605	neutral	None	None	None	None	N
K/C	0.7526	likely_pathogenic	0.8409	pathogenic	-0.295	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
K/D	0.7852	likely_pathogenic	0.848	pathogenic	0.053	Stabilizing	1.0	D	0.653	neutral	None	None	None	None	N
K/E	0.3724	ambiguous	0.4813	ambiguous	0.082	Stabilizing	0.999	D	0.589	neutral	N	0.507493804	None	None	N
K/F	0.897	likely_pathogenic	0.9364	pathogenic	-0.301	Destabilizing	1.0	D	0.629	neutral	None	None	None	None	N
K/G	0.6901	likely_pathogenic	0.7886	pathogenic	-0.357	Destabilizing	1.0	D	0.567	neutral	None	None	None	None	N
K/H	0.3904	ambiguous	0.465	ambiguous	-0.611	Destabilizing	1.0	D	0.609	neutral	None	None	None	None	N
K/I	0.4531	ambiguous	0.5588	ambiguous	0.359	Stabilizing	1.0	D	0.639	neutral	N	0.471484143	None	None	N
K/L	0.5163	ambiguous	0.6257	pathogenic	0.359	Stabilizing	1.0	D	0.567	neutral	None	None	None	None	N
K/M	0.3548	ambiguous	0.458	ambiguous	0.063	Stabilizing	1.0	D	0.608	neutral	None	None	None	None	N
K/N	0.6375	likely_pathogenic	0.7334	pathogenic	0.108	Stabilizing	1.0	D	0.684	prob.neutral	N	0.476128498	None	None	N
K/P	0.7777	likely_pathogenic	0.8317	pathogenic	0.22	Stabilizing	1.0	D	0.63	neutral	None	None	None	None	N
K/Q	0.1923	likely_benign	0.2413	benign	-0.005	Destabilizing	1.0	D	0.683	prob.neutral	N	0.468722212	None	None	N
K/R	0.087	likely_benign	0.1	benign	-0.099	Destabilizing	0.999	D	0.514	neutral	N	0.468481949	None	None	N
K/S	0.5922	likely_pathogenic	0.6922	pathogenic	-0.375	Destabilizing	0.999	D	0.631	neutral	None	None	None	None	N
K/T	0.2901	likely_benign	0.3777	ambiguous	-0.186	Destabilizing	1.0	D	0.629	neutral	N	0.47339302	None	None	N
K/V	0.4573	ambiguous	0.5563	ambiguous	0.22	Stabilizing	1.0	D	0.619	neutral	None	None	None	None	N
K/W	0.8651	likely_pathogenic	0.9167	pathogenic	-0.322	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
K/Y	0.7613	likely_pathogenic	0.8429	pathogenic	0.021	Stabilizing	1.0	D	0.634	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.