TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29383	88372;88373;88374	chr2:178557007;178557006;178557005	chr2:179421734;179421733;179421732
N2AB	27742	83449;83450;83451	chr2:178557007;178557006;178557005	chr2:179421734;179421733;179421732
N2A	26815	80668;80669;80670	chr2:178557007;178557006;178557005	chr2:179421734;179421733;179421732
N2B	20318	61177;61178;61179	chr2:178557007;178557006;178557005	chr2:179421734;179421733;179421732
Novex-1	20443	61552;61553;61554	chr2:178557007;178557006;178557005	chr2:179421734;179421733;179421732
Novex-2	20510	61753;61754;61755	chr2:178557007;178557006;178557005	chr2:179421734;179421733;179421732
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: Fn3-102
• Domain position: 49
• Structural Position: 66
• Q(SASA): 0.4016
• 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	rs2154155238	None	0.062	N	0.297	0.166	0.292062946507	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
T/S	rs2154155238	None	0.001	N	0.101	0.083	0.0762999501168	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-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
T/A	0.0879	likely_benign	0.0825	benign	-0.918	Destabilizing	None	N	0.087	neutral	N	0.45479547	None	None	N
T/C	0.3519	ambiguous	0.3441	ambiguous	-0.605	Destabilizing	0.824	D	0.342	neutral	None	None	None	None	N
T/D	0.5631	ambiguous	0.5036	ambiguous	0.005	Stabilizing	0.149	N	0.327	neutral	None	None	None	None	N
T/E	0.3702	ambiguous	0.3164	benign	0.03	Stabilizing	0.149	N	0.263	neutral	None	None	None	None	N
T/F	0.3317	likely_benign	0.2586	benign	-0.87	Destabilizing	0.001	N	0.267	neutral	None	None	None	None	N
T/G	0.2488	likely_benign	0.2376	benign	-1.196	Destabilizing	0.035	N	0.311	neutral	None	None	None	None	N
T/H	0.3005	likely_benign	0.2651	benign	-1.335	Destabilizing	0.935	D	0.313	neutral	None	None	None	None	N
T/I	0.1533	likely_benign	0.1258	benign	-0.263	Destabilizing	0.062	N	0.297	neutral	N	0.413026205	None	None	N
T/K	0.2895	likely_benign	0.236	benign	-0.658	Destabilizing	0.149	N	0.276	neutral	None	None	None	None	N
T/L	0.096	likely_benign	0.0847	benign	-0.263	Destabilizing	0.035	N	0.348	neutral	None	None	None	None	N
T/M	0.0769	likely_benign	0.0723	benign	-0.109	Destabilizing	0.555	D	0.35	neutral	None	None	None	None	N
T/N	0.1332	likely_benign	0.127	benign	-0.642	Destabilizing	0.117	N	0.299	neutral	N	0.456795625	None	None	N
T/P	0.593	likely_pathogenic	0.5447	ambiguous	-0.449	Destabilizing	0.317	N	0.379	neutral	N	0.509611389	None	None	N
T/Q	0.2093	likely_benign	0.193	benign	-0.759	Destabilizing	0.555	D	0.381	neutral	None	None	None	None	N
T/R	0.2538	likely_benign	0.1998	benign	-0.455	Destabilizing	0.38	N	0.378	neutral	None	None	None	None	N
T/S	0.1172	likely_benign	0.1135	benign	-1.0	Destabilizing	0.001	N	0.101	neutral	N	0.426763506	None	None	N
T/V	0.1178	likely_benign	0.1024	benign	-0.449	Destabilizing	0.002	N	0.131	neutral	None	None	None	None	N
T/W	0.6835	likely_pathogenic	0.5979	pathogenic	-0.771	Destabilizing	0.935	D	0.342	neutral	None	None	None	None	N
T/Y	0.3466	ambiguous	0.2849	benign	-0.548	Destabilizing	0.235	N	0.348	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.