TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31463	94612;94613;94614	chr2:178547138;178547137;178547136	chr2:179411865;179411864;179411863
N2AB	29822	89689;89690;89691	chr2:178547138;178547137;178547136	chr2:179411865;179411864;179411863
N2A	28895	86908;86909;86910	chr2:178547138;178547137;178547136	chr2:179411865;179411864;179411863
N2B	22398	67417;67418;67419	chr2:178547138;178547137;178547136	chr2:179411865;179411864;179411863
Novex-1	22523	67792;67793;67794	chr2:178547138;178547137;178547136	chr2:179411865;179411864;179411863
Novex-2	22590	67993;67994;67995	chr2:178547138;178547137;178547136	chr2:179411865;179411864;179411863
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Fn3-117
• Domain position: 56
• Structural Position: 77
• Q(SASA): 0.1137
• 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
C/G	None	None	1.0	N	0.758	0.499	0.782932109435	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
C/Y	rs760317660	-1.374	1.0	N	0.819	0.383	0.676867754606	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	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
C/A	0.4483	ambiguous	0.4913	ambiguous	-1.676	Destabilizing	0.998	D	0.544	neutral	None	None	None	None	N
C/D	0.9264	likely_pathogenic	0.9513	pathogenic	-0.964	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
C/E	0.94	likely_pathogenic	0.9595	pathogenic	-0.751	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
C/F	0.3828	ambiguous	0.4513	ambiguous	-1.02	Destabilizing	1.0	D	0.807	deleterious	N	0.503453421	None	None	N
C/G	0.3745	ambiguous	0.4199	ambiguous	-2.029	Highly Destabilizing	1.0	D	0.758	deleterious	N	0.446559988	None	None	N
C/H	0.7986	likely_pathogenic	0.8602	pathogenic	-2.032	Highly Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
C/I	0.3268	likely_benign	0.3496	ambiguous	-0.72	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
C/K	0.9354	likely_pathogenic	0.9597	pathogenic	-0.899	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
C/L	0.3943	ambiguous	0.4431	ambiguous	-0.72	Destabilizing	0.999	D	0.565	neutral	None	None	None	None	N
C/M	0.6096	likely_pathogenic	0.6354	pathogenic	0.37	Stabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
C/N	0.742	likely_pathogenic	0.7958	pathogenic	-1.424	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
C/P	0.9695	likely_pathogenic	0.9698	pathogenic	-1.017	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
C/Q	0.8283	likely_pathogenic	0.8749	pathogenic	-1.016	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
C/R	0.7374	likely_pathogenic	0.8297	pathogenic	-1.187	Destabilizing	1.0	D	0.837	deleterious	N	0.498276888	None	None	N
C/S	0.3701	ambiguous	0.4357	ambiguous	-1.806	Destabilizing	1.0	D	0.707	prob.neutral	N	0.470876856	None	None	N
C/T	0.474	ambiguous	0.506	ambiguous	-1.402	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
C/V	0.2634	likely_benign	0.2752	benign	-1.017	Destabilizing	0.999	D	0.625	neutral	None	None	None	None	N
C/W	0.8122	likely_pathogenic	0.8618	pathogenic	-1.273	Destabilizing	1.0	D	0.813	deleterious	N	0.481546548	None	None	N
C/Y	0.5852	likely_pathogenic	0.68	pathogenic	-1.137	Destabilizing	1.0	D	0.819	deleterious	N	0.498796963	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.