TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29151	87676;87677;87678	chr2:178557903;178557902;178557901	chr2:179422630;179422629;179422628
N2AB	27510	82753;82754;82755	chr2:178557903;178557902;178557901	chr2:179422630;179422629;179422628
N2A	26583	79972;79973;79974	chr2:178557903;178557902;178557901	chr2:179422630;179422629;179422628
N2B	20086	60481;60482;60483	chr2:178557903;178557902;178557901	chr2:179422630;179422629;179422628
Novex-1	20211	60856;60857;60858	chr2:178557903;178557902;178557901	chr2:179422630;179422629;179422628
Novex-2	20278	61057;61058;61059	chr2:178557903;178557902;178557901	chr2:179422630;179422629;179422628
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: Fn3-100
• Domain position: 15
• Structural Position: 16
• Q(SASA): 0.286
• 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	None	None	0.971	N	0.524	0.439	0.357724736475	gnomAD-4.0.0	1.59194E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85783E-06	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	0.1644	likely_benign	0.1911	benign	-0.846	Destabilizing	0.489	N	0.493	neutral	N	0.478084416	None	None	N
T/C	0.5287	ambiguous	0.537	ambiguous	-0.614	Destabilizing	0.998	D	0.515	neutral	None	None	None	None	N
T/D	0.4635	ambiguous	0.5088	ambiguous	-0.393	Destabilizing	0.754	D	0.481	neutral	None	None	None	None	N
T/E	0.577	likely_pathogenic	0.6599	pathogenic	-0.372	Destabilizing	0.86	D	0.481	neutral	None	None	None	None	N
T/F	0.5955	likely_pathogenic	0.6609	pathogenic	-0.825	Destabilizing	0.978	D	0.59	neutral	None	None	None	None	N
T/G	0.2143	likely_benign	0.2396	benign	-1.127	Destabilizing	0.754	D	0.471	neutral	None	None	None	None	N
T/H	0.4294	ambiguous	0.4869	ambiguous	-1.378	Destabilizing	0.994	D	0.569	neutral	None	None	None	None	N
T/I	0.6728	likely_pathogenic	0.739	pathogenic	-0.184	Destabilizing	0.971	D	0.524	neutral	N	0.504533237	None	None	N
T/K	0.3788	ambiguous	0.4552	ambiguous	-0.757	Destabilizing	0.754	D	0.482	neutral	None	None	None	None	N
T/L	0.2114	likely_benign	0.2635	benign	-0.184	Destabilizing	0.86	D	0.478	neutral	None	None	None	None	N
T/M	0.1458	likely_benign	0.1787	benign	0.061	Stabilizing	0.998	D	0.497	neutral	None	None	None	None	N
T/N	0.1601	likely_benign	0.1686	benign	-0.779	Destabilizing	0.126	N	0.274	neutral	N	0.510998256	None	None	N
T/P	0.6701	likely_pathogenic	0.7608	pathogenic	-0.372	Destabilizing	0.971	D	0.523	neutral	N	0.519510393	None	None	N
T/Q	0.3699	ambiguous	0.425	ambiguous	-0.932	Destabilizing	0.956	D	0.529	neutral	None	None	None	None	N
T/R	0.3308	likely_benign	0.3958	ambiguous	-0.543	Destabilizing	0.956	D	0.525	neutral	None	None	None	None	N
T/S	0.0945	likely_benign	0.0973	benign	-1.063	Destabilizing	0.058	N	0.267	neutral	N	0.444407905	None	None	N
T/V	0.4581	ambiguous	0.5274	ambiguous	-0.372	Destabilizing	0.86	D	0.503	neutral	None	None	None	None	N
T/W	0.8483	likely_pathogenic	0.8678	pathogenic	-0.749	Destabilizing	0.998	D	0.596	neutral	None	None	None	None	N
T/Y	0.6148	likely_pathogenic	0.6613	pathogenic	-0.511	Destabilizing	0.993	D	0.591	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.