TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6509	19750;19751;19752	chr2:178728299;178728298;178728297	chr2:179593026;179593025;179593024
N2AB	6192	18799;18800;18801	chr2:178728299;178728298;178728297	chr2:179593026;179593025;179593024
N2A	5265	16018;16019;16020	chr2:178728299;178728298;178728297	chr2:179593026;179593025;179593024
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: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-49
• Domain position: 29
• Structural Position: 43
• Q(SASA): 0.5217
• 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
P/L	None	None	0.967	N	0.671	0.531	0.698156398671	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
P/S	rs764314153	-0.896	0.892	N	0.526	0.519	0.479056812784	gnomAD-2.1.1	8.08E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.79E-05	0
P/S	rs764314153	-0.896	0.892	N	0.526	0.519	0.479056812784	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	0	4.77555E-04
P/S	rs764314153	-0.896	0.892	N	0.526	0.519	0.479056812784	gnomAD-4.0.0	3.09976E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.54342E-06	1.09837E-05	1.60226E-05

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
P/A	0.5325	ambiguous	0.458	ambiguous	-0.404	Destabilizing	0.892	D	0.515	neutral	N	0.503290059	None	None	I
P/C	0.9537	likely_pathogenic	0.9366	pathogenic	-0.733	Destabilizing	0.999	D	0.718	prob.delet.	None	None	None	None	I
P/D	0.8552	likely_pathogenic	0.8059	pathogenic	-0.044	Destabilizing	0.975	D	0.508	neutral	None	None	None	None	I
P/E	0.7998	likely_pathogenic	0.7315	pathogenic	-0.145	Destabilizing	0.845	D	0.551	neutral	None	None	None	None	I
P/F	0.9525	likely_pathogenic	0.9249	pathogenic	-0.582	Destabilizing	0.997	D	0.683	prob.neutral	None	None	None	None	I
P/G	0.781	likely_pathogenic	0.7563	pathogenic	-0.526	Destabilizing	0.975	D	0.587	neutral	None	None	None	None	I
P/H	0.7744	likely_pathogenic	0.7024	pathogenic	-0.052	Destabilizing	0.12	N	0.531	neutral	D	0.539297986	None	None	I
P/I	0.9079	likely_pathogenic	0.8793	pathogenic	-0.229	Destabilizing	0.987	D	0.696	prob.neutral	None	None	None	None	I
P/K	0.8738	likely_pathogenic	0.843	pathogenic	-0.385	Destabilizing	0.845	D	0.52	neutral	None	None	None	None	I
P/L	0.6373	likely_pathogenic	0.5447	ambiguous	-0.229	Destabilizing	0.967	D	0.671	neutral	N	0.499037325	None	None	I
P/M	0.8944	likely_pathogenic	0.8611	pathogenic	-0.447	Destabilizing	0.999	D	0.648	neutral	None	None	None	None	I
P/N	0.8301	likely_pathogenic	0.7851	pathogenic	-0.186	Destabilizing	0.975	D	0.654	neutral	None	None	None	None	I
P/Q	0.7178	likely_pathogenic	0.6454	pathogenic	-0.373	Destabilizing	0.496	N	0.471	neutral	None	None	None	None	I
P/R	0.7568	likely_pathogenic	0.694	pathogenic	0.063	Stabilizing	0.967	D	0.655	neutral	N	0.499860245	None	None	I
P/S	0.6662	likely_pathogenic	0.5855	pathogenic	-0.576	Destabilizing	0.892	D	0.526	neutral	N	0.49498517399999997	None	None	I
P/T	0.6219	likely_pathogenic	0.557	ambiguous	-0.571	Destabilizing	0.983	D	0.518	neutral	N	0.48738785	None	None	I
P/V	0.8138	likely_pathogenic	0.7715	pathogenic	-0.254	Destabilizing	0.987	D	0.643	neutral	None	None	None	None	I
P/W	0.9735	likely_pathogenic	0.9584	pathogenic	-0.657	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	I
P/Y	0.9312	likely_pathogenic	0.9017	pathogenic	-0.368	Destabilizing	0.95	D	0.696	prob.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.