TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29195	87808;87809;87810	chr2:178557771;178557770;178557769	chr2:179422498;179422497;179422496
N2AB	27554	82885;82886;82887	chr2:178557771;178557770;178557769	chr2:179422498;179422497;179422496
N2A	26627	80104;80105;80106	chr2:178557771;178557770;178557769	chr2:179422498;179422497;179422496
N2B	20130	60613;60614;60615	chr2:178557771;178557770;178557769	chr2:179422498;179422497;179422496
Novex-1	20255	60988;60989;60990	chr2:178557771;178557770;178557769	chr2:179422498;179422497;179422496
Novex-2	20322	61189;61190;61191	chr2:178557771;178557770;178557769	chr2:179422498;179422497;179422496
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: Fn3-100
• Domain position: 59
• Structural Position: 89
• Q(SASA): 0.2655
• 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/N	rs751134822	-1.055	None	N	0.231	0.186	0.223847106136	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
T/N	rs751134822	-1.055	None	N	0.231	0.186	0.223847106136	gnomAD-4.0.0	2.0525E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	3.47818E-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	0.0977	likely_benign	0.118	benign	-0.668	Destabilizing	0.005	N	0.295	neutral	N	0.491069655	None	None	N
T/C	0.2123	likely_benign	0.2187	benign	-0.432	Destabilizing	None	N	0.292	neutral	None	None	None	None	N
T/D	0.5062	ambiguous	0.5096	ambiguous	-0.899	Destabilizing	0.016	N	0.46	neutral	None	None	None	None	N
T/E	0.4833	ambiguous	0.4957	ambiguous	-0.721	Destabilizing	0.038	N	0.465	neutral	None	None	None	None	N
T/F	0.4775	ambiguous	0.5275	ambiguous	-0.551	Destabilizing	0.356	N	0.592	neutral	None	None	None	None	N
T/G	0.2009	likely_benign	0.2087	benign	-1.044	Destabilizing	0.016	N	0.449	neutral	None	None	None	None	N
T/H	0.2885	likely_benign	0.3026	benign	-1.09	Destabilizing	0.214	N	0.585	neutral	None	None	None	None	N
T/I	0.4322	ambiguous	0.4927	ambiguous	0.299	Stabilizing	0.055	N	0.497	neutral	N	0.515668371	None	None	N
T/K	0.2842	likely_benign	0.3051	benign	-0.26	Destabilizing	0.038	N	0.469	neutral	None	None	None	None	N
T/L	0.1347	likely_benign	0.1789	benign	0.299	Stabilizing	0.031	N	0.427	neutral	None	None	None	None	N
T/M	0.1255	likely_benign	0.159	benign	0.115	Stabilizing	0.628	D	0.539	neutral	None	None	None	None	N
T/N	0.0847	likely_benign	0.0982	benign	-0.92	Destabilizing	None	N	0.231	neutral	N	0.476826514	None	None	N
T/P	0.0801	likely_benign	0.0843	benign	0.008	Stabilizing	0.106	N	0.56	neutral	N	0.468179234	None	None	N
T/Q	0.2576	likely_benign	0.2674	benign	-0.697	Destabilizing	0.214	N	0.572	neutral	None	None	None	None	N
T/R	0.2391	likely_benign	0.2657	benign	-0.397	Destabilizing	0.072	N	0.495	neutral	None	None	None	None	N
T/S	0.1025	likely_benign	0.1156	benign	-1.148	Destabilizing	None	N	0.236	neutral	N	0.492284197	None	None	N
T/V	0.2688	likely_benign	0.3146	benign	0.008	Stabilizing	0.031	N	0.365	neutral	None	None	None	None	N
T/W	0.7764	likely_pathogenic	0.7634	pathogenic	-0.784	Destabilizing	0.864	D	0.616	neutral	None	None	None	None	N
T/Y	0.3859	ambiguous	0.4257	ambiguous	-0.33	Destabilizing	0.356	N	0.587	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.