TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9910	29953;29954;29955	chr2:178704744;178704743;178704742	chr2:179569471;179569470;179569469
N2AB	9593	29002;29003;29004	chr2:178704744;178704743;178704742	chr2:179569471;179569470;179569469
N2A	8666	26221;26222;26223	chr2:178704744;178704743;178704742	chr2:179569471;179569470;179569469
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: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-84
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.3347
• 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/R	None	None	0.959	None	0.394	0.347	0.480198768302	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
T/A	0.3458	ambiguous	0.2564	benign	-0.452	Destabilizing	0.116	N	0.058	neutral	None	None	None	None	N
T/C	0.9134	likely_pathogenic	0.8886	pathogenic	-0.335	Destabilizing	1.0	D	0.39	neutral	None	None	None	None	N
T/D	0.8714	likely_pathogenic	0.7822	pathogenic	0.289	Stabilizing	0.969	D	0.309	neutral	None	None	None	None	N
T/E	0.7052	likely_pathogenic	0.5592	ambiguous	0.241	Stabilizing	0.939	D	0.312	neutral	None	None	None	None	N
T/F	0.8053	likely_pathogenic	0.6842	pathogenic	-0.784	Destabilizing	0.999	D	0.425	neutral	None	None	None	None	N
T/G	0.8719	likely_pathogenic	0.8222	pathogenic	-0.631	Destabilizing	0.927	D	0.311	neutral	None	None	None	None	N
T/H	0.7418	likely_pathogenic	0.6027	pathogenic	-0.912	Destabilizing	0.995	D	0.409	neutral	None	None	None	None	N
T/I	0.5671	likely_pathogenic	0.4294	ambiguous	-0.092	Destabilizing	0.994	D	0.393	neutral	None	None	None	None	N
T/K	0.6539	likely_pathogenic	0.4997	ambiguous	-0.424	Destabilizing	0.921	D	0.319	neutral	None	None	None	None	N
T/L	0.4484	ambiguous	0.3335	benign	-0.092	Destabilizing	0.969	D	0.312	neutral	None	None	None	None	N
T/M	0.2407	likely_benign	0.1679	benign	0.024	Stabilizing	0.999	D	0.395	neutral	None	None	None	None	N
T/N	0.5166	ambiguous	0.378	ambiguous	-0.268	Destabilizing	0.969	D	0.299	neutral	None	None	None	None	N
T/P	0.7989	likely_pathogenic	0.7445	pathogenic	-0.181	Destabilizing	0.994	D	0.391	neutral	None	None	None	None	N
T/Q	0.647	likely_pathogenic	0.4926	ambiguous	-0.447	Destabilizing	0.736	D	0.184	neutral	None	None	None	None	N
T/R	0.6063	likely_pathogenic	0.45	ambiguous	-0.195	Destabilizing	0.959	D	0.394	neutral	None	None	None	None	N
T/S	0.4477	ambiguous	0.3375	benign	-0.524	Destabilizing	0.276	N	0.073	neutral	None	None	None	None	N
T/V	0.4208	ambiguous	0.3206	benign	-0.181	Destabilizing	0.969	D	0.246	neutral	None	None	None	None	N
T/W	0.9371	likely_pathogenic	0.904	pathogenic	-0.765	Destabilizing	1.0	D	0.482	neutral	None	None	None	None	N
T/Y	0.7829	likely_pathogenic	0.6917	pathogenic	-0.494	Destabilizing	0.999	D	0.425	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.