TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29377	88354;88355;88356	chr2:178557025;178557024;178557023	chr2:179421752;179421751;179421750
N2AB	27736	83431;83432;83433	chr2:178557025;178557024;178557023	chr2:179421752;179421751;179421750
N2A	26809	80650;80651;80652	chr2:178557025;178557024;178557023	chr2:179421752;179421751;179421750
N2B	20312	61159;61160;61161	chr2:178557025;178557024;178557023	chr2:179421752;179421751;179421750
Novex-1	20437	61534;61535;61536	chr2:178557025;178557024;178557023	chr2:179421752;179421751;179421750
Novex-2	20504	61735;61736;61737	chr2:178557025;178557024;178557023	chr2:179421752;179421751;179421750
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-102
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.3666
• 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
L/F	rs908918470	-1.617	0.901	N	0.517	0.177	0.593429312994	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
L/F	rs908918470	-1.617	0.901	N	0.517	0.177	0.593429312994	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
L/F	rs908918470	-1.617	0.901	N	0.517	0.177	0.593429312994	gnomAD-4.0.0	3.84335E-06	None	None	None	None	N	None	5.07271E-05	0	None	0	0	None	0	0	0	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
L/A	0.3709	ambiguous	0.32	benign	-2.059	Highly Destabilizing	0.415	N	0.443	neutral	None	None	None	None	N
L/C	0.5258	ambiguous	0.4852	ambiguous	-1.121	Destabilizing	0.996	D	0.575	neutral	None	None	None	None	N
L/D	0.8666	likely_pathogenic	0.825	pathogenic	-1.693	Destabilizing	0.961	D	0.675	neutral	None	None	None	None	N
L/E	0.6629	likely_pathogenic	0.6101	pathogenic	-1.673	Destabilizing	0.987	D	0.678	prob.neutral	None	None	None	None	N
L/F	0.2075	likely_benign	0.1718	benign	-1.446	Destabilizing	0.901	D	0.517	neutral	N	0.476750836	None	None	N
L/G	0.6434	likely_pathogenic	0.5728	pathogenic	-2.408	Highly Destabilizing	0.005	N	0.357	neutral	None	None	None	None	N
L/H	0.3572	ambiguous	0.3159	benign	-1.588	Destabilizing	0.995	D	0.678	prob.neutral	N	0.513017054	None	None	N
L/I	0.0892	likely_benign	0.0915	benign	-1.145	Destabilizing	0.008	N	0.18	neutral	N	0.504416213	None	None	N
L/K	0.4624	ambiguous	0.4276	ambiguous	-1.377	Destabilizing	0.961	D	0.642	neutral	None	None	None	None	N
L/M	0.144	likely_benign	0.1392	benign	-0.824	Destabilizing	0.923	D	0.514	neutral	None	None	None	None	N
L/N	0.5216	ambiguous	0.4851	ambiguous	-1.164	Destabilizing	0.961	D	0.68	prob.neutral	None	None	None	None	N
L/P	0.7419	likely_pathogenic	0.6854	pathogenic	-1.422	Destabilizing	0.983	D	0.679	prob.neutral	N	0.494892653	None	None	N
L/Q	0.3134	likely_benign	0.2834	benign	-1.368	Destabilizing	0.987	D	0.672	neutral	None	None	None	None	N
L/R	0.3635	ambiguous	0.3249	benign	-0.735	Destabilizing	0.983	D	0.666	neutral	N	0.475483388	None	None	N
L/S	0.4255	ambiguous	0.3679	ambiguous	-1.783	Destabilizing	0.775	D	0.592	neutral	None	None	None	None	N
L/T	0.3254	likely_benign	0.3019	benign	-1.656	Destabilizing	0.775	D	0.509	neutral	None	None	None	None	N
L/V	0.106	likely_benign	0.1039	benign	-1.422	Destabilizing	0.156	N	0.428	neutral	N	0.440364735	None	None	N
L/W	0.4304	ambiguous	0.3822	ambiguous	-1.529	Destabilizing	0.996	D	0.69	prob.neutral	None	None	None	None	N
L/Y	0.4424	ambiguous	0.3844	ambiguous	-1.344	Destabilizing	0.961	D	0.556	neutral	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.