TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18001	54226;54227;54228	chr2:178605176;178605175;178605174	chr2:179469903;179469902;179469901
N2AB	16360	49303;49304;49305	chr2:178605176;178605175;178605174	chr2:179469903;179469902;179469901
N2A	15433	46522;46523;46524	chr2:178605176;178605175;178605174	chr2:179469903;179469902;179469901
N2B	8936	27031;27032;27033	chr2:178605176;178605175;178605174	chr2:179469903;179469902;179469901
Novex-1	9061	27406;27407;27408	chr2:178605176;178605175;178605174	chr2:179469903;179469902;179469901
Novex-2	9128	27607;27608;27609	chr2:178605176;178605175;178605174	chr2:179469903;179469902;179469901
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-114
• Domain position: 34
• Structural Position: 49
• Q(SASA): 0.2051
• 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
S/T	None	None	0.062	N	0.521	0.044	0.110078149338	gnomAD-4.0.0	1.59413E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86266E-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
S/A	0.0928	likely_benign	0.0884	benign	-0.957	Destabilizing	None	N	0.215	neutral	N	0.490878408	None	None	N
S/C	0.123	likely_benign	0.1188	benign	-0.749	Destabilizing	0.78	D	0.529	neutral	N	0.471238702	None	None	N
S/D	0.6681	likely_pathogenic	0.675	pathogenic	-1.017	Destabilizing	0.001	N	0.329	neutral	None	None	None	None	N
S/E	0.5715	likely_pathogenic	0.5496	ambiguous	-0.892	Destabilizing	0.081	N	0.51	neutral	None	None	None	None	N
S/F	0.2485	likely_benign	0.2331	benign	-1.097	Destabilizing	0.317	N	0.618	neutral	N	0.425536063	None	None	N
S/G	0.1406	likely_benign	0.1458	benign	-1.284	Destabilizing	0.035	N	0.509	neutral	None	None	None	None	N
S/H	0.352	ambiguous	0.3377	benign	-1.711	Destabilizing	0.555	D	0.537	neutral	None	None	None	None	N
S/I	0.226	likely_benign	0.1828	benign	-0.153	Destabilizing	0.235	N	0.59	neutral	None	None	None	None	N
S/K	0.5635	ambiguous	0.5697	pathogenic	-0.278	Destabilizing	0.149	N	0.497	neutral	None	None	None	None	N
S/L	0.096	likely_benign	0.091	benign	-0.153	Destabilizing	0.001	N	0.416	neutral	None	None	None	None	N
S/M	0.1511	likely_benign	0.1495	benign	-0.064	Destabilizing	0.38	N	0.538	neutral	None	None	None	None	N
S/N	0.2132	likely_benign	0.207	benign	-0.742	Destabilizing	0.001	N	0.341	neutral	None	None	None	None	N
S/P	0.9889	likely_pathogenic	0.9893	pathogenic	-0.388	Destabilizing	0.317	N	0.562	neutral	N	0.470985212	None	None	N
S/Q	0.4001	ambiguous	0.3901	ambiguous	-0.7	Destabilizing	0.555	D	0.559	neutral	None	None	None	None	N
S/R	0.5324	ambiguous	0.5137	ambiguous	-0.492	Destabilizing	0.38	N	0.557	neutral	None	None	None	None	N
S/T	0.0791	likely_benign	0.0846	benign	-0.57	Destabilizing	0.062	N	0.521	neutral	N	0.409838679	None	None	N
S/V	0.2106	likely_benign	0.1822	benign	-0.388	Destabilizing	0.081	N	0.545	neutral	None	None	None	None	N
S/W	0.4187	ambiguous	0.4054	ambiguous	-1.187	Destabilizing	0.935	D	0.654	neutral	None	None	None	None	N
S/Y	0.2407	likely_benign	0.221	benign	-0.794	Destabilizing	0.484	N	0.605	neutral	N	0.421669039	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.