TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29294	88105;88106;88107	chr2:178557382;178557381;178557380	chr2:179422109;179422108;179422107
N2AB	27653	83182;83183;83184	chr2:178557382;178557381;178557380	chr2:179422109;179422108;179422107
N2A	26726	80401;80402;80403	chr2:178557382;178557381;178557380	chr2:179422109;179422108;179422107
N2B	20229	60910;60911;60912	chr2:178557382;178557381;178557380	chr2:179422109;179422108;179422107
Novex-1	20354	61285;61286;61287	chr2:178557382;178557381;178557380	chr2:179422109;179422108;179422107
Novex-2	20421	61486;61487;61488	chr2:178557382;178557381;178557380	chr2:179422109;179422108;179422107
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-101
• Domain position: 58
• Structural Position: 88
• Q(SASA): 0.5162
• 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
T/I	None	None	0.988	N	0.417	0.344	0.510172456258	gnomAD-4.0.0	6.84156E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99418E-07	0	0
T/K	None	None	0.92	N	0.41	0.337	0.442261297928	gnomAD-4.0.0	6.84156E-07	None	None	None	None	I	None	0	0	None	3.82673E-05	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
T/A	0.0774	likely_benign	0.0852	benign	-0.856	Destabilizing	0.061	N	0.144	neutral	N	0.417608092	None	None	I
T/C	0.4041	ambiguous	0.5197	ambiguous	-0.483	Destabilizing	0.999	D	0.477	neutral	None	None	None	None	I
T/D	0.3435	ambiguous	0.3697	ambiguous	-0.593	Destabilizing	0.939	D	0.402	neutral	None	None	None	None	I
T/E	0.36	ambiguous	0.3856	ambiguous	-0.469	Destabilizing	0.939	D	0.42	neutral	None	None	None	None	I
T/F	0.4516	ambiguous	0.4985	ambiguous	-0.824	Destabilizing	0.997	D	0.527	neutral	None	None	None	None	I
T/G	0.1751	likely_benign	0.1839	benign	-1.183	Destabilizing	0.759	D	0.409	neutral	None	None	None	None	I
T/H	0.2963	likely_benign	0.3425	ambiguous	-1.181	Destabilizing	0.999	D	0.533	neutral	None	None	None	None	I
T/I	0.4969	ambiguous	0.5511	ambiguous	-0.033	Destabilizing	0.988	D	0.417	neutral	N	0.482929007	None	None	I
T/K	0.3429	ambiguous	0.3741	ambiguous	-0.445	Destabilizing	0.92	D	0.41	neutral	N	0.450181871	None	None	I
T/L	0.1776	likely_benign	0.2019	benign	-0.033	Destabilizing	0.939	D	0.355	neutral	None	None	None	None	I
T/M	0.1107	likely_benign	0.1301	benign	-0.102	Destabilizing	0.999	D	0.482	neutral	None	None	None	None	I
T/N	0.0986	likely_benign	0.1032	benign	-0.849	Destabilizing	0.939	D	0.391	neutral	None	None	None	None	I
T/P	0.3785	ambiguous	0.3715	ambiguous	-0.277	Destabilizing	0.988	D	0.431	neutral	N	0.496452878	None	None	I
T/Q	0.2485	likely_benign	0.275	benign	-0.731	Destabilizing	0.991	D	0.473	neutral	None	None	None	None	I
T/R	0.3182	likely_benign	0.3631	ambiguous	-0.413	Destabilizing	0.988	D	0.433	neutral	N	0.467690196	None	None	I
T/S	0.0879	likely_benign	0.0967	benign	-1.123	Destabilizing	0.31	N	0.159	neutral	N	0.433286834	None	None	I
T/V	0.2987	likely_benign	0.3478	ambiguous	-0.277	Destabilizing	0.939	D	0.313	neutral	None	None	None	None	I
T/W	0.786	likely_pathogenic	0.8201	pathogenic	-0.959	Destabilizing	0.999	D	0.62	neutral	None	None	None	None	I
T/Y	0.4123	ambiguous	0.4597	ambiguous	-0.595	Destabilizing	0.997	D	0.529	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.