TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31377	94354;94355;94356	chr2:178547497;178547496;178547495	chr2:179412224;179412223;179412222
N2AB	29736	89431;89432;89433	chr2:178547497;178547496;178547495	chr2:179412224;179412223;179412222
N2A	28809	86650;86651;86652	chr2:178547497;178547496;178547495	chr2:179412224;179412223;179412222
N2B	22312	67159;67160;67161	chr2:178547497;178547496;178547495	chr2:179412224;179412223;179412222
Novex-1	22437	67534;67535;67536	chr2:178547497;178547496;178547495	chr2:179412224;179412223;179412222
Novex-2	22504	67735;67736;67737	chr2:178547497;178547496;178547495	chr2:179412224;179412223;179412222
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: Fn3-116
• Domain position: 70
• Structural Position: 102
• Q(SASA): 0.502
• 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	0.055	N	0.291	0.209	0.301122078929	gnomAD-4.0.0	1.59257E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02682E-05

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	0.2873	likely_benign	0.2924	benign	-2.06	Highly Destabilizing	0.016	N	0.303	neutral	None	None	None	None	N
M/C	0.5346	ambiguous	0.5249	ambiguous	-1.364	Destabilizing	0.864	D	0.356	neutral	None	None	None	None	N
M/D	0.8435	likely_pathogenic	0.87	pathogenic	-0.811	Destabilizing	0.072	N	0.471	neutral	None	None	None	None	N
M/E	0.3953	ambiguous	0.4108	ambiguous	-0.739	Destabilizing	0.016	N	0.294	neutral	None	None	None	None	N
M/F	0.535	ambiguous	0.5657	pathogenic	-0.845	Destabilizing	0.214	N	0.313	neutral	None	None	None	None	N
M/G	0.5081	ambiguous	0.5267	ambiguous	-2.416	Highly Destabilizing	0.072	N	0.414	neutral	None	None	None	None	N
M/H	0.4333	ambiguous	0.4299	ambiguous	-1.484	Destabilizing	0.356	N	0.398	neutral	None	None	None	None	N
M/I	0.4687	ambiguous	0.4901	ambiguous	-1.11	Destabilizing	0.029	N	0.219	neutral	N	0.479904558	None	None	N
M/K	0.1065	likely_benign	0.1053	benign	-0.863	Destabilizing	None	N	0.136	neutral	N	0.413871567	None	None	N
M/L	0.1774	likely_benign	0.1783	benign	-1.11	Destabilizing	None	N	0.069	neutral	N	0.4797312	None	None	N
M/N	0.5034	ambiguous	0.5091	ambiguous	-0.776	Destabilizing	0.072	N	0.442	neutral	None	None	None	None	N
M/P	0.9769	likely_pathogenic	0.9807	pathogenic	-1.402	Destabilizing	0.356	N	0.449	neutral	None	None	None	None	N
M/Q	0.1247	likely_benign	0.1124	benign	-0.789	Destabilizing	0.001	N	0.196	neutral	None	None	None	None	N
M/R	0.1209	likely_benign	0.1237	benign	-0.434	Destabilizing	0.029	N	0.323	neutral	N	0.439132584	None	None	N
M/S	0.3168	likely_benign	0.3195	benign	-1.427	Destabilizing	0.016	N	0.294	neutral	None	None	None	None	N
M/T	0.1548	likely_benign	0.1524	benign	-1.244	Destabilizing	0.055	N	0.291	neutral	N	0.396413596	None	None	N
M/V	0.1004	likely_benign	0.0994	benign	-1.402	Destabilizing	0.012	N	0.284	neutral	N	0.42903302	None	None	N
M/W	0.6956	likely_pathogenic	0.7111	pathogenic	-0.822	Destabilizing	0.864	D	0.361	neutral	None	None	None	None	N
M/Y	0.6632	likely_pathogenic	0.695	pathogenic	-0.888	Destabilizing	0.628	D	0.414	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.