TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26530	79813;79814;79815	chr2:178566544;178566543;178566542	chr2:179431271;179431270;179431269
N2AB	24889	74890;74891;74892	chr2:178566544;178566543;178566542	chr2:179431271;179431270;179431269
N2A	23962	72109;72110;72111	chr2:178566544;178566543;178566542	chr2:179431271;179431270;179431269
N2B	17465	52618;52619;52620	chr2:178566544;178566543;178566542	chr2:179431271;179431270;179431269
Novex-1	17590	52993;52994;52995	chr2:178566544;178566543;178566542	chr2:179431271;179431270;179431269
Novex-2	17657	53194;53195;53196	chr2:178566544;178566543;178566542	chr2:179431271;179431270;179431269
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-81
• Domain position: 44
• Structural Position: 54
• Q(SASA): 1.0325
• 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
D/V	None	None	0.983	N	0.591	0.419	0.36076525451	gnomAD-4.0.0	1.59226E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85878E-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
D/A	0.0917	likely_benign	0.0973	benign	-0.145	Destabilizing	0.805	D	0.436	neutral	N	0.462827802	None	None	N
D/C	0.4127	ambiguous	0.4398	ambiguous	0.101	Stabilizing	0.999	D	0.664	neutral	None	None	None	None	N
D/E	0.0865	likely_benign	0.0902	benign	-0.294	Destabilizing	0.025	N	0.305	neutral	N	0.414284494	None	None	N
D/F	0.4494	ambiguous	0.4642	ambiguous	-0.288	Destabilizing	0.999	D	0.572	neutral	None	None	None	None	N
D/G	0.0884	likely_benign	0.0932	benign	-0.29	Destabilizing	0.025	N	0.347	neutral	N	0.384574875	None	None	N
D/H	0.1907	likely_benign	0.215	benign	0.027	Stabilizing	0.995	D	0.447	neutral	N	0.453249805	None	None	N
D/I	0.2104	likely_benign	0.231	benign	0.174	Stabilizing	0.987	D	0.583	neutral	None	None	None	None	N
D/K	0.1889	likely_benign	0.2184	benign	0.379	Stabilizing	0.845	D	0.414	neutral	None	None	None	None	N
D/L	0.2288	likely_benign	0.2542	benign	0.174	Stabilizing	0.975	D	0.589	neutral	None	None	None	None	N
D/M	0.3638	ambiguous	0.3818	ambiguous	0.238	Stabilizing	0.999	D	0.607	neutral	None	None	None	None	N
D/N	0.0731	likely_benign	0.0732	benign	0.251	Stabilizing	0.892	D	0.397	neutral	N	0.451666659	None	None	N
D/P	0.3965	ambiguous	0.4447	ambiguous	0.088	Stabilizing	0.987	D	0.462	neutral	None	None	None	None	N
D/Q	0.1888	likely_benign	0.2083	benign	0.234	Stabilizing	0.95	D	0.427	neutral	None	None	None	None	N
D/R	0.2579	likely_benign	0.2892	benign	0.537	Stabilizing	0.975	D	0.513	neutral	None	None	None	None	N
D/S	0.083	likely_benign	0.082	benign	0.124	Stabilizing	0.916	D	0.425	neutral	None	None	None	None	N
D/T	0.1194	likely_benign	0.1255	benign	0.228	Stabilizing	0.975	D	0.413	neutral	None	None	None	None	N
D/V	0.1295	likely_benign	0.1425	benign	0.088	Stabilizing	0.983	D	0.591	neutral	N	0.498615244	None	None	N
D/W	0.7504	likely_pathogenic	0.7807	pathogenic	-0.234	Destabilizing	0.999	D	0.68	prob.neutral	None	None	None	None	N
D/Y	0.2023	likely_benign	0.2234	benign	-0.065	Destabilizing	0.999	D	0.571	neutral	N	0.456719299	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.