TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5112	15559;15560;15561	chr2:178734490;178734489;178734488	chr2:179599217;179599216;179599215
N2AB	4795	14608;14609;14610	chr2:178734490;178734489;178734488	chr2:179599217;179599216;179599215
N2A	3868	11827;11828;11829	chr2:178734490;178734489;178734488	chr2:179599217;179599216;179599215
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-34
• Domain position: 38
• Structural Position: 52
• Q(SASA): 0.9583
• 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/N	None	None	0.999	N	0.681	0.358	0.32714864917	gnomAD-4.0.0	4.77456E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	4.29997E-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	0.5733	likely_pathogenic	0.6421	pathogenic	0.041	Stabilizing	0.998	D	0.581	neutral	None	None	None	None	I
K/C	0.781	likely_pathogenic	0.8339	pathogenic	-0.253	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
K/D	0.6389	likely_pathogenic	0.7026	pathogenic	0.034	Stabilizing	1.0	D	0.649	neutral	None	None	None	None	I
K/E	0.2734	likely_benign	0.3211	benign	0.055	Stabilizing	0.996	D	0.595	neutral	N	0.482765252	None	None	I
K/F	0.907	likely_pathogenic	0.9367	pathogenic	-0.126	Destabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	I
K/G	0.3437	ambiguous	0.3857	ambiguous	-0.159	Destabilizing	1.0	D	0.564	neutral	None	None	None	None	I
K/H	0.3444	ambiguous	0.3893	ambiguous	-0.324	Destabilizing	1.0	D	0.637	neutral	None	None	None	None	I
K/I	0.7832	likely_pathogenic	0.8328	pathogenic	0.494	Stabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	I
K/L	0.6394	likely_pathogenic	0.7073	pathogenic	0.494	Stabilizing	1.0	D	0.564	neutral	None	None	None	None	I
K/M	0.4896	ambiguous	0.5578	ambiguous	0.101	Stabilizing	1.0	D	0.64	neutral	D	0.605456906	None	None	I
K/N	0.4634	ambiguous	0.5321	ambiguous	0.189	Stabilizing	0.999	D	0.681	prob.neutral	N	0.467812705	None	None	I
K/P	0.9086	likely_pathogenic	0.9244	pathogenic	0.371	Stabilizing	1.0	D	0.621	neutral	None	None	None	None	I
K/Q	0.1498	likely_benign	0.1659	benign	0.075	Stabilizing	0.999	D	0.683	prob.neutral	N	0.519291441	None	None	I
K/R	0.0747	likely_benign	0.0756	benign	-0.003	Destabilizing	0.64	D	0.369	neutral	N	0.5094837	None	None	I
K/S	0.4928	ambiguous	0.5537	ambiguous	-0.253	Destabilizing	0.998	D	0.599	neutral	None	None	None	None	I
K/T	0.4001	ambiguous	0.461	ambiguous	-0.084	Destabilizing	0.999	D	0.626	neutral	N	0.521338364	None	None	I
K/V	0.7304	likely_pathogenic	0.7878	pathogenic	0.371	Stabilizing	1.0	D	0.611	neutral	None	None	None	None	I
K/W	0.8252	likely_pathogenic	0.8648	pathogenic	-0.182	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	I
K/Y	0.7853	likely_pathogenic	0.8339	pathogenic	0.168	Stabilizing	1.0	D	0.631	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.