TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19621	59086;59087;59088	chr2:178593347;178593346;178593345	chr2:179458074;179458073;179458072
N2AB	17980	54163;54164;54165	chr2:178593347;178593346;178593345	chr2:179458074;179458073;179458072
N2A	17053	51382;51383;51384	chr2:178593347;178593346;178593345	chr2:179458074;179458073;179458072
N2B	10556	31891;31892;31893	chr2:178593347;178593346;178593345	chr2:179458074;179458073;179458072
Novex-1	10681	32266;32267;32268	chr2:178593347;178593346;178593345	chr2:179458074;179458073;179458072
Novex-2	10748	32467;32468;32469	chr2:178593347;178593346;178593345	chr2:179458074;179458073;179458072
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Fn3-30
• Domain position: 43
• Structural Position: 54
• Q(SASA): 0.8562
• 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
M/T	None	None	0.324	N	0.345	0.136	0.528761452848	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-06	0	0
M/V	None	None	0.165	N	0.361	0.175	0.495773158881	gnomAD-4.0.0	1.59208E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85966E-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
M/A	0.2202	likely_benign	0.1975	benign	-0.154	Destabilizing	0.116	N	0.342	neutral	None	None	None	None	N
M/C	0.6358	likely_pathogenic	0.613	pathogenic	-0.403	Destabilizing	0.981	D	0.267	neutral	None	None	None	None	N
M/D	0.5708	likely_pathogenic	0.5525	ambiguous	0.392	Stabilizing	0.388	N	0.355	neutral	None	None	None	None	N
M/E	0.3563	ambiguous	0.3394	benign	0.323	Stabilizing	0.241	N	0.337	neutral	None	None	None	None	N
M/F	0.3697	ambiguous	0.3419	ambiguous	-0.214	Destabilizing	0.818	D	0.259	neutral	None	None	None	None	N
M/G	0.3362	likely_benign	0.3041	benign	-0.222	Destabilizing	0.388	N	0.373	neutral	None	None	None	None	N
M/H	0.3666	ambiguous	0.3052	benign	0.366	Stabilizing	0.818	D	0.275	neutral	None	None	None	None	N
M/I	0.4339	ambiguous	0.3935	ambiguous	-0.075	Destabilizing	0.492	N	0.325	neutral	N	0.470322282	None	None	N
M/K	0.133	likely_benign	0.0973	benign	0.436	Stabilizing	0.001	N	0.171	neutral	N	0.369445999	None	None	N
M/L	0.1307	likely_benign	0.117	benign	-0.075	Destabilizing	0.079	N	0.253	neutral	N	0.413602208	None	None	N
M/N	0.2759	likely_benign	0.2514	benign	0.557	Stabilizing	0.388	N	0.344	neutral	None	None	None	None	N
M/P	0.7588	likely_pathogenic	0.7233	pathogenic	-0.08	Destabilizing	0.818	D	0.337	neutral	None	None	None	None	N
M/Q	0.1664	likely_benign	0.1394	benign	0.409	Stabilizing	0.241	N	0.291	neutral	None	None	None	None	N
M/R	0.1826	likely_benign	0.135	benign	0.821	Stabilizing	0.001	N	0.267	neutral	N	0.40455865	None	None	N
M/S	0.2213	likely_benign	0.1969	benign	0.164	Stabilizing	0.241	N	0.321	neutral	None	None	None	None	N
M/T	0.137	likely_benign	0.1194	benign	0.179	Stabilizing	0.324	N	0.345	neutral	N	0.396208526	None	None	N
M/V	0.0998	likely_benign	0.0893	benign	-0.08	Destabilizing	0.165	N	0.361	neutral	N	0.42939838	None	None	N
M/W	0.6479	likely_pathogenic	0.6115	pathogenic	-0.239	Destabilizing	0.981	D	0.297	neutral	None	None	None	None	N
M/Y	0.4883	ambiguous	0.4556	ambiguous	-0.026	Destabilizing	0.818	D	0.281	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.