TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15868	47827;47828;47829	chr2:178617483;178617482;178617481	chr2:179482210;179482209;179482208
N2AB	14227	42904;42905;42906	chr2:178617483;178617482;178617481	chr2:179482210;179482209;179482208
N2A	13300	40123;40124;40125	chr2:178617483;178617482;178617481	chr2:179482210;179482209;179482208
N2B	6803	20632;20633;20634	chr2:178617483;178617482;178617481	chr2:179482210;179482209;179482208
Novex-1	6928	21007;21008;21009	chr2:178617483;178617482;178617481	chr2:179482210;179482209;179482208
Novex-2	6995	21208;21209;21210	chr2:178617483;178617482;178617481	chr2:179482210;179482209;179482208
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: Fn3-3
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.2105
• 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/Y	None	None	None	N	0.381	0.067	0.340273420219	gnomAD-4.0.0	2.0808E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.71182E-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	0.0652	likely_benign	0.0658	benign	-0.565	Destabilizing	None	N	0.119	neutral	N	0.313911399	None	None	N
S/C	0.0783	likely_benign	0.0784	benign	-0.479	Destabilizing	0.295	N	0.533	neutral	N	0.422000009	None	None	N
S/D	0.3468	ambiguous	0.4307	ambiguous	0.374	Stabilizing	0.072	N	0.455	neutral	None	None	None	None	N
S/E	0.4241	ambiguous	0.4891	ambiguous	0.38	Stabilizing	0.031	N	0.426	neutral	None	None	None	None	N
S/F	0.1169	likely_benign	0.1412	benign	-0.886	Destabilizing	0.029	N	0.501	neutral	N	0.392885555	None	None	N
S/G	0.1155	likely_benign	0.1273	benign	-0.798	Destabilizing	0.007	N	0.335	neutral	None	None	None	None	N
S/H	0.1697	likely_benign	0.191	benign	-1.219	Destabilizing	None	N	0.244	neutral	None	None	None	None	N
S/I	0.1146	likely_benign	0.1342	benign	-0.059	Destabilizing	0.072	N	0.56	neutral	None	None	None	None	N
S/K	0.504	ambiguous	0.6048	pathogenic	-0.352	Destabilizing	0.031	N	0.435	neutral	None	None	None	None	N
S/L	0.1214	likely_benign	0.1469	benign	-0.059	Destabilizing	0.016	N	0.377	neutral	None	None	None	None	N
S/M	0.2103	likely_benign	0.2402	benign	-0.031	Destabilizing	0.356	N	0.523	neutral	None	None	None	None	N
S/N	0.1551	likely_benign	0.1925	benign	-0.401	Destabilizing	0.072	N	0.462	neutral	None	None	None	None	N
S/P	0.131	likely_benign	0.1399	benign	-0.194	Destabilizing	0.055	N	0.566	neutral	N	0.450841314	None	None	N
S/Q	0.3704	ambiguous	0.4202	ambiguous	-0.439	Destabilizing	0.072	N	0.477	neutral	None	None	None	None	N
S/R	0.4245	ambiguous	0.501	ambiguous	-0.372	Destabilizing	0.072	N	0.5	neutral	None	None	None	None	N
S/T	0.0968	likely_benign	0.105	benign	-0.435	Destabilizing	0.012	N	0.415	neutral	N	0.450472985	None	None	N
S/V	0.1175	likely_benign	0.1293	benign	-0.194	Destabilizing	0.016	N	0.417	neutral	None	None	None	None	N
S/W	0.1775	likely_benign	0.2102	benign	-0.892	Destabilizing	None	N	0.433	neutral	None	None	None	None	N
S/Y	0.0832	likely_benign	0.0955	benign	-0.572	Destabilizing	None	N	0.381	neutral	N	0.419436645	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.