TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23484	70675;70676;70677	chr2:178575682;178575681;178575680	chr2:179440409;179440408;179440407
N2AB	21843	65752;65753;65754	chr2:178575682;178575681;178575680	chr2:179440409;179440408;179440407
N2A	20916	62971;62972;62973	chr2:178575682;178575681;178575680	chr2:179440409;179440408;179440407
N2B	14419	43480;43481;43482	chr2:178575682;178575681;178575680	chr2:179440409;179440408;179440407
Novex-1	14544	43855;43856;43857	chr2:178575682;178575681;178575680	chr2:179440409;179440408;179440407
Novex-2	14611	44056;44057;44058	chr2:178575682;178575681;178575680	chr2:179440409;179440408;179440407
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-58
• Domain position: 50
• Structural Position: 67
• Q(SASA): 0.4136
• 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/K	rs1178437079	-0.547	0.65	N	0.463	0.173	0.353125101423	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.59E-05	None	0	None	0	0	0
T/K	rs1178437079	-0.547	0.65	N	0.463	0.173	0.353125101423	gnomAD-4.0.0	6.84284E-07	None	None	None	None	N	None	0	0	None	0	2.52283E-05	None	0	0	0	0	0
T/R	None	None	0.972	N	0.533	0.312	0.427940940899	gnomAD-4.0.0	6.84284E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99546E-07	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	0.0856	likely_benign	0.0826	benign	-0.676	Destabilizing	0.051	N	0.373	neutral	N	0.474056021	None	None	N
T/C	0.4703	ambiguous	0.4559	ambiguous	-0.382	Destabilizing	0.993	D	0.521	neutral	None	None	None	None	N
T/D	0.8044	likely_pathogenic	0.7823	pathogenic	-0.153	Destabilizing	0.92	D	0.51	neutral	None	None	None	None	N
T/E	0.6494	likely_pathogenic	0.6359	pathogenic	-0.203	Destabilizing	0.781	D	0.482	neutral	None	None	None	None	N
T/F	0.4498	ambiguous	0.4247	ambiguous	-0.959	Destabilizing	0.958	D	0.551	neutral	None	None	None	None	N
T/G	0.4312	ambiguous	0.3919	ambiguous	-0.868	Destabilizing	0.9	D	0.49	neutral	None	None	None	None	N
T/H	0.5463	ambiguous	0.5156	ambiguous	-1.171	Destabilizing	0.995	D	0.546	neutral	None	None	None	None	N
T/I	0.1613	likely_benign	0.1654	benign	-0.272	Destabilizing	0.277	N	0.441	neutral	N	0.503917568	None	None	N
T/K	0.5344	ambiguous	0.4973	ambiguous	-0.643	Destabilizing	0.65	D	0.463	neutral	N	0.516884078	None	None	N
T/L	0.117	likely_benign	0.1074	benign	-0.272	Destabilizing	0.149	N	0.416	neutral	None	None	None	None	N
T/M	0.0998	likely_benign	0.1009	benign	0.074	Stabilizing	0.182	N	0.356	neutral	None	None	None	None	N
T/N	0.2884	likely_benign	0.2599	benign	-0.456	Destabilizing	0.79	D	0.447	neutral	None	None	None	None	N
T/P	0.1644	likely_benign	0.1457	benign	-0.377	Destabilizing	0.896	D	0.525	neutral	N	0.520905818	None	None	N
T/Q	0.4372	ambiguous	0.4132	ambiguous	-0.72	Destabilizing	0.891	D	0.536	neutral	None	None	None	None	N
T/R	0.4799	ambiguous	0.4393	ambiguous	-0.312	Destabilizing	0.972	D	0.533	neutral	N	0.50522429	None	None	N
T/S	0.1804	likely_benign	0.1696	benign	-0.707	Destabilizing	0.115	N	0.381	neutral	N	0.501837268	None	None	N
T/V	0.107	likely_benign	0.1079	benign	-0.377	Destabilizing	0.01	N	0.114	neutral	None	None	None	None	N
T/W	0.8335	likely_pathogenic	0.8288	pathogenic	-0.886	Destabilizing	0.998	D	0.586	neutral	None	None	None	None	N
T/Y	0.5584	ambiguous	0.5444	ambiguous	-0.654	Destabilizing	0.979	D	0.563	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.