TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9675	29248;29249;29250	chr2:178707544;178707543;178707542	chr2:179572271;179572270;179572269
N2AB	9358	28297;28298;28299	chr2:178707544;178707543;178707542	chr2:179572271;179572270;179572269
N2A	8431	25516;25517;25518	chr2:178707544;178707543;178707542	chr2:179572271;179572270;179572269
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-82
• Domain position: 86
• Structural Position: 172
• Q(SASA): 0.0939
• 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/A	None	None	None	None	0.115	0.096	0.0611884634855	gnomAD-4.0.0	1.59258E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86107E-06	0	0
S/L	None	None	0.027	None	0.65	0.238	0.437100570223	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.0626	likely_benign	0.0576	benign	-0.814	Destabilizing	None	N	0.115	neutral	None	None	None	None	N
S/C	0.0622	likely_benign	0.0741	benign	-0.565	Destabilizing	0.001	N	0.455	neutral	None	None	None	None	N
S/D	0.8879	likely_pathogenic	0.8771	pathogenic	-0.767	Destabilizing	0.149	N	0.641	neutral	None	None	None	None	N
S/E	0.9185	likely_pathogenic	0.9086	pathogenic	-0.659	Destabilizing	0.149	N	0.601	neutral	None	None	None	None	N
S/F	0.5921	likely_pathogenic	0.512	ambiguous	-0.717	Destabilizing	0.555	D	0.752	deleterious	None	None	None	None	N
S/G	0.0948	likely_benign	0.1	benign	-1.166	Destabilizing	0.035	N	0.543	neutral	None	None	None	None	N
S/H	0.8246	likely_pathogenic	0.7902	pathogenic	-1.568	Destabilizing	0.935	D	0.707	prob.neutral	None	None	None	None	N
S/I	0.4473	ambiguous	0.367	ambiguous	0.047	Stabilizing	0.081	N	0.684	prob.neutral	None	None	None	None	N
S/K	0.9734	likely_pathogenic	0.9641	pathogenic	-0.503	Destabilizing	0.149	N	0.597	neutral	None	None	None	None	N
S/L	0.2879	likely_benign	0.2154	benign	0.047	Stabilizing	0.027	N	0.65	neutral	None	None	None	None	N
S/M	0.4495	ambiguous	0.3765	ambiguous	0.139	Stabilizing	0.555	D	0.723	prob.delet.	None	None	None	None	N
S/N	0.5078	ambiguous	0.4769	ambiguous	-0.833	Destabilizing	0.262	N	0.633	neutral	None	None	None	None	N
S/P	0.931	likely_pathogenic	0.9063	pathogenic	-0.204	Destabilizing	0.317	N	0.752	deleterious	None	None	None	None	N
S/Q	0.8795	likely_pathogenic	0.8599	pathogenic	-0.775	Destabilizing	0.555	D	0.666	neutral	None	None	None	None	N
S/R	0.9465	likely_pathogenic	0.9278	pathogenic	-0.674	Destabilizing	0.38	N	0.753	deleterious	None	None	None	None	N
S/T	0.1575	likely_benign	0.1362	benign	-0.681	Destabilizing	0.027	N	0.535	neutral	None	None	None	None	N
S/V	0.3187	likely_benign	0.2735	benign	-0.204	Destabilizing	0.002	N	0.46	neutral	None	None	None	None	N
S/W	0.7805	likely_pathogenic	0.7078	pathogenic	-0.811	Destabilizing	0.935	D	0.747	deleterious	None	None	None	None	N
S/Y	0.5623	ambiguous	0.4869	ambiguous	-0.458	Destabilizing	0.555	D	0.756	deleterious	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.