TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31884	95875;95876;95877	chr2:178545460;178545459;178545458	chr2:179410187;179410186;179410185
N2AB	30243	90952;90953;90954	chr2:178545460;178545459;178545458	chr2:179410187;179410186;179410185
N2A	29316	88171;88172;88173	chr2:178545460;178545459;178545458	chr2:179410187;179410186;179410185
N2B	22819	68680;68681;68682	chr2:178545460;178545459;178545458	chr2:179410187;179410186;179410185
Novex-1	22944	69055;69056;69057	chr2:178545460;178545459;178545458	chr2:179410187;179410186;179410185
Novex-2	23011	69256;69257;69258	chr2:178545460;178545459;178545458	chr2:179410187;179410186;179410185
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-120
• Domain position: 78
• Structural Position: 109
• Q(SASA): 0.1457
• 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
T/I	rs977811552	-0.133	0.211	N	0.564	0.209	0.329020015101	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	5.81E-05	None	0	0	None	0	None	0	0	0
T/I	rs977811552	-0.133	0.211	N	0.564	0.209	0.329020015101	gnomAD-4.0.0	6.38457E-06	None	None	None	None	N	None	0	6.86625E-05	None	0	0	None	0	0	2.87127E-06	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
T/A	0.1012	likely_benign	0.1007	benign	-1.326	Destabilizing	0.64	D	0.729	prob.delet.	N	0.421778974	None	None	N
T/C	0.3011	likely_benign	0.3091	benign	-1.484	Destabilizing	0.999	D	0.764	deleterious	None	None	None	None	N
T/D	0.7858	likely_pathogenic	0.8024	pathogenic	-2.538	Highly Destabilizing	0.976	D	0.776	deleterious	None	None	None	None	N
T/E	0.6179	likely_pathogenic	0.6386	pathogenic	-2.359	Highly Destabilizing	0.976	D	0.77	deleterious	None	None	None	None	N
T/F	0.3139	likely_benign	0.3189	benign	-1.016	Destabilizing	0.988	D	0.817	deleterious	None	None	None	None	N
T/G	0.4176	ambiguous	0.413	ambiguous	-1.649	Destabilizing	0.851	D	0.769	deleterious	None	None	None	None	N
T/H	0.4362	ambiguous	0.4208	ambiguous	-1.626	Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
T/I	0.2668	likely_benign	0.281	benign	-0.494	Destabilizing	0.211	N	0.564	neutral	N	0.45135252	None	None	N
T/K	0.5548	ambiguous	0.5149	ambiguous	-0.959	Destabilizing	0.976	D	0.773	deleterious	None	None	None	None	N
T/L	0.1442	likely_benign	0.1482	benign	-0.494	Destabilizing	0.851	D	0.729	prob.delet.	None	None	None	None	N
T/M	0.0931	likely_benign	0.0927	benign	-0.676	Destabilizing	0.997	D	0.781	deleterious	None	None	None	None	N
T/N	0.2808	likely_benign	0.2783	benign	-1.677	Destabilizing	0.968	D	0.743	deleterious	N	0.474344526	None	None	N
T/P	0.9532	likely_pathogenic	0.9435	pathogenic	-0.745	Destabilizing	0.984	D	0.793	deleterious	N	0.486714789	None	None	N
T/Q	0.4055	ambiguous	0.3833	ambiguous	-1.56	Destabilizing	0.988	D	0.802	deleterious	None	None	None	None	N
T/R	0.4464	ambiguous	0.3904	ambiguous	-0.963	Destabilizing	0.976	D	0.797	deleterious	None	None	None	None	N
T/S	0.1247	likely_benign	0.1237	benign	-1.734	Destabilizing	0.103	N	0.354	neutral	N	0.393883084	None	None	N
T/V	0.1827	likely_benign	0.1962	benign	-0.745	Destabilizing	0.851	D	0.715	prob.delet.	None	None	None	None	N
T/W	0.6544	likely_pathogenic	0.6513	pathogenic	-1.239	Destabilizing	0.999	D	0.776	deleterious	None	None	None	None	N
T/Y	0.3494	ambiguous	0.3619	ambiguous	-0.856	Destabilizing	0.996	D	0.839	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.