TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27824	83695;83696;83697	chr2:178562662;178562661;178562660	chr2:179427389;179427388;179427387
N2AB	26183	78772;78773;78774	chr2:178562662;178562661;178562660	chr2:179427389;179427388;179427387
N2A	25256	75991;75992;75993	chr2:178562662;178562661;178562660	chr2:179427389;179427388;179427387
N2B	18759	56500;56501;56502	chr2:178562662;178562661;178562660	chr2:179427389;179427388;179427387
Novex-1	18884	56875;56876;56877	chr2:178562662;178562661;178562660	chr2:179427389;179427388;179427387
Novex-2	18951	57076;57077;57078	chr2:178562662;178562661;178562660	chr2:179427389;179427388;179427387
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: Fn3-90
• Domain position: 59
• Structural Position: 90
• Q(SASA): 0.2606
• 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	0.012	N	0.371	0.118	0.242825505644	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-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	0.07	likely_benign	0.0714	benign	-0.954	Destabilizing	0.005	N	0.285	neutral	N	0.51775087	None	None	N
T/C	0.2777	likely_benign	0.307	benign	-0.483	Destabilizing	0.356	N	0.459	neutral	None	None	None	None	N
T/D	0.4436	ambiguous	0.4593	ambiguous	-0.141	Destabilizing	0.038	N	0.399	neutral	None	None	None	None	N
T/E	0.4994	ambiguous	0.5087	ambiguous	-0.061	Destabilizing	0.016	N	0.389	neutral	None	None	None	None	N
T/F	0.1863	likely_benign	0.1806	benign	-0.783	Destabilizing	0.214	N	0.548	neutral	None	None	None	None	N
T/G	0.147	likely_benign	0.158	benign	-1.29	Destabilizing	0.016	N	0.39	neutral	None	None	None	None	N
T/H	0.2669	likely_benign	0.2611	benign	-1.42	Destabilizing	0.214	N	0.499	neutral	None	None	None	None	N
T/I	0.1452	likely_benign	0.1285	benign	-0.122	Destabilizing	0.012	N	0.371	neutral	N	0.473347475	None	None	N
T/K	0.4722	ambiguous	0.4579	ambiguous	-0.542	Destabilizing	0.016	N	0.387	neutral	None	None	None	None	N
T/L	0.1022	likely_benign	0.0935	benign	-0.122	Destabilizing	None	N	0.241	neutral	None	None	None	None	N
T/M	0.0968	likely_benign	0.0923	benign	-0.012	Destabilizing	0.214	N	0.462	neutral	None	None	None	None	N
T/N	0.1016	likely_benign	0.0997	benign	-0.686	Destabilizing	None	N	0.166	neutral	N	0.464321817	None	None	N
T/P	0.5129	ambiguous	0.5234	ambiguous	-0.366	Destabilizing	0.055	N	0.487	neutral	N	0.477373173	None	None	N
T/Q	0.3187	likely_benign	0.3167	benign	-0.675	Destabilizing	0.072	N	0.525	neutral	None	None	None	None	N
T/R	0.4148	ambiguous	0.404	ambiguous	-0.489	Destabilizing	0.072	N	0.48	neutral	None	None	None	None	N
T/S	0.0665	likely_benign	0.0683	benign	-1.037	Destabilizing	None	N	0.163	neutral	N	0.396477885	None	None	N
T/V	0.1108	likely_benign	0.0983	benign	-0.366	Destabilizing	None	N	0.17	neutral	None	None	None	None	N
T/W	0.5903	likely_pathogenic	0.6012	pathogenic	-0.759	Destabilizing	0.864	D	0.53	neutral	None	None	None	None	N
T/Y	0.2416	likely_benign	0.242	benign	-0.492	Destabilizing	0.356	N	0.52	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.