TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29295	88108;88109;88110	chr2:178557379;178557378;178557377	chr2:179422106;179422105;179422104
N2AB	27654	83185;83186;83187	chr2:178557379;178557378;178557377	chr2:179422106;179422105;179422104
N2A	26727	80404;80405;80406	chr2:178557379;178557378;178557377	chr2:179422106;179422105;179422104
N2B	20230	60913;60914;60915	chr2:178557379;178557378;178557377	chr2:179422106;179422105;179422104
Novex-1	20355	61288;61289;61290	chr2:178557379;178557378;178557377	chr2:179422106;179422105;179422104
Novex-2	20422	61489;61490;61491	chr2:178557379;178557378;178557377	chr2:179422106;179422105;179422104
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-101
• Domain position: 59
• Structural Position: 89
• Q(SASA): 0.2896
• 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/S	None	None	0.103	N	0.344	0.354	0.178374595973	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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	0.1075	likely_benign	0.1162	benign	-0.729	Destabilizing	0.64	D	0.424	neutral	N	0.492830855	None	None	I
T/C	0.3917	ambiguous	0.4649	ambiguous	-0.431	Destabilizing	0.999	D	0.617	neutral	None	None	None	None	I
T/D	0.6532	likely_pathogenic	0.6482	pathogenic	-1.17	Destabilizing	0.851	D	0.503	neutral	None	None	None	None	I
T/E	0.6485	likely_pathogenic	0.6322	pathogenic	-0.988	Destabilizing	0.919	D	0.525	neutral	None	None	None	None	I
T/F	0.6821	likely_pathogenic	0.6758	pathogenic	-0.485	Destabilizing	0.996	D	0.684	prob.neutral	None	None	None	None	I
T/G	0.277	likely_benign	0.2907	benign	-1.124	Destabilizing	0.851	D	0.535	neutral	None	None	None	None	I
T/H	0.4564	ambiguous	0.4621	ambiguous	-1.305	Destabilizing	0.997	D	0.677	prob.neutral	None	None	None	None	I
T/I	0.5089	ambiguous	0.5273	ambiguous	0.3	Stabilizing	0.984	D	0.621	neutral	N	0.511748486	None	None	I
T/K	0.3361	likely_benign	0.3465	ambiguous	-0.484	Destabilizing	0.919	D	0.522	neutral	None	None	None	None	I
T/L	0.1655	likely_benign	0.193	benign	0.3	Stabilizing	0.919	D	0.519	neutral	None	None	None	None	I
T/M	0.1563	likely_benign	0.1703	benign	0.212	Stabilizing	0.999	D	0.617	neutral	None	None	None	None	I
T/N	0.1488	likely_benign	0.149	benign	-1.109	Destabilizing	0.103	N	0.241	neutral	N	0.491998389	None	None	I
T/P	0.1566	likely_benign	0.1712	benign	-0.012	Destabilizing	0.984	D	0.622	neutral	N	0.490415	None	None	I
T/Q	0.3347	likely_benign	0.3347	benign	-0.858	Destabilizing	0.988	D	0.631	neutral	None	None	None	None	I
T/R	0.2749	likely_benign	0.2943	benign	-0.687	Destabilizing	0.976	D	0.619	neutral	None	None	None	None	I
T/S	0.1327	likely_benign	0.1342	benign	-1.282	Destabilizing	0.103	N	0.344	neutral	N	0.494832318	None	None	I
T/V	0.2999	likely_benign	0.3255	benign	-0.012	Destabilizing	0.919	D	0.438	neutral	None	None	None	None	I
T/W	0.8913	likely_pathogenic	0.8981	pathogenic	-0.764	Destabilizing	0.999	D	0.652	neutral	None	None	None	None	I
T/Y	0.6335	likely_pathogenic	0.6286	pathogenic	-0.329	Destabilizing	0.996	D	0.683	prob.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.