TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24183	72772;72773;72774	chr2:178573585;178573584;178573583	chr2:179438312;179438311;179438310
N2AB	22542	67849;67850;67851	chr2:178573585;178573584;178573583	chr2:179438312;179438311;179438310
N2A	21615	65068;65069;65070	chr2:178573585;178573584;178573583	chr2:179438312;179438311;179438310
N2B	15118	45577;45578;45579	chr2:178573585;178573584;178573583	chr2:179438312;179438311;179438310
Novex-1	15243	45952;45953;45954	chr2:178573585;178573584;178573583	chr2:179438312;179438311;179438310
Novex-2	15310	46153;46154;46155	chr2:178573585;178573584;178573583	chr2:179438312;179438311;179438310
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-63
• Domain position: 62
• Structural Position: 92
• Q(SASA): 0.3883
• 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/N	None	None	1.0	N	0.736	0.351	0.214338557667	gnomAD-4.0.0	7.43133E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.45035E-07	0	0
K/T	None	None	1.0	N	0.823	0.358	0.340753184043	gnomAD-4.0.0	7.42424E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.44444E-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	0.6098	likely_pathogenic	0.7269	pathogenic	-0.165	Destabilizing	0.999	D	0.743	deleterious	None	None	None	None	N
K/C	0.8083	likely_pathogenic	0.8499	pathogenic	-0.411	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
K/D	0.8765	likely_pathogenic	0.9216	pathogenic	0.044	Stabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
K/E	0.5384	ambiguous	0.6873	pathogenic	0.111	Stabilizing	0.999	D	0.593	neutral	N	0.518364159	None	None	N
K/F	0.9088	likely_pathogenic	0.9325	pathogenic	-0.025	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
K/G	0.7946	likely_pathogenic	0.8561	pathogenic	-0.462	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
K/H	0.4175	ambiguous	0.4871	ambiguous	-0.69	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
K/I	0.543	ambiguous	0.6267	pathogenic	0.566	Stabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
K/L	0.5791	likely_pathogenic	0.6605	pathogenic	0.566	Stabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
K/M	0.395	ambiguous	0.4915	ambiguous	0.227	Stabilizing	1.0	D	0.797	deleterious	N	0.481661906	None	None	N
K/N	0.7179	likely_pathogenic	0.8073	pathogenic	-0.184	Destabilizing	1.0	D	0.736	prob.delet.	N	0.501914626	None	None	N
K/P	0.793	likely_pathogenic	0.8419	pathogenic	0.353	Stabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
K/Q	0.2583	likely_benign	0.338	benign	-0.263	Destabilizing	1.0	D	0.703	prob.neutral	N	0.50568565	None	None	N
K/R	0.1021	likely_benign	0.1087	benign	-0.35	Destabilizing	0.999	D	0.567	neutral	N	0.488524041	None	None	N
K/S	0.6952	likely_pathogenic	0.796	pathogenic	-0.722	Destabilizing	0.999	D	0.661	neutral	None	None	None	None	N
K/T	0.2887	likely_benign	0.3904	ambiguous	-0.475	Destabilizing	1.0	D	0.823	deleterious	N	0.440052517	None	None	N
K/V	0.4851	ambiguous	0.5663	pathogenic	0.353	Stabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
K/W	0.8449	likely_pathogenic	0.8779	pathogenic	0.015	Stabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
K/Y	0.7972	likely_pathogenic	0.8445	pathogenic	0.32	Stabilizing	1.0	D	0.851	deleterious	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.