TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33781	101566;101567;101568	chr2:178535274;178535273;178535272	chr2:179400001;179400000;179399999
N2AB	32140	96643;96644;96645	chr2:178535274;178535273;178535272	chr2:179400001;179400000;179399999
N2A	31213	93862;93863;93864	chr2:178535274;178535273;178535272	chr2:179400001;179400000;179399999
N2B	24716	74371;74372;74373	chr2:178535274;178535273;178535272	chr2:179400001;179400000;179399999
Novex-1	24841	74746;74747;74748	chr2:178535274;178535273;178535272	chr2:179400001;179400000;179399999
Novex-2	24908	74947;74948;74949	chr2:178535274;178535273;178535272	chr2:179400001;179400000;179399999
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Fn3-132
• Domain position: 93
• Structural Position: 128
• Q(SASA): 0.3467
• 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
I/V	rs1029128193	None	None	N	0.074	0.137	0.141422826196	gnomAD-4.0.0	4.77324E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.57334E-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
I/A	0.281	likely_benign	0.2645	benign	-0.834	Destabilizing	0.005	N	0.378	neutral	None	None	None	None	N
I/C	0.6573	likely_pathogenic	0.6346	pathogenic	-0.642	Destabilizing	0.283	N	0.489	neutral	None	None	None	None	N
I/D	0.6714	likely_pathogenic	0.6354	pathogenic	0.086	Stabilizing	0.101	N	0.609	neutral	None	None	None	None	N
I/E	0.4676	ambiguous	0.4552	ambiguous	0.017	Stabilizing	0.077	N	0.574	neutral	None	None	None	None	N
I/F	0.1969	likely_benign	0.1775	benign	-0.757	Destabilizing	0.022	N	0.423	neutral	None	None	None	None	N
I/G	0.6266	likely_pathogenic	0.5743	pathogenic	-1.035	Destabilizing	0.101	N	0.558	neutral	None	None	None	None	N
I/H	0.5158	ambiguous	0.5021	ambiguous	-0.358	Destabilizing	0.653	D	0.515	neutral	None	None	None	None	N
I/K	0.3458	ambiguous	0.342	ambiguous	-0.306	Destabilizing	0.002	N	0.603	neutral	N	0.422515267	None	None	N
I/L	0.1362	likely_benign	0.1084	benign	-0.416	Destabilizing	None	N	0.279	neutral	N	0.421475117	None	None	N
I/M	0.1074	likely_benign	0.099	benign	-0.311	Destabilizing	0.017	N	0.501	neutral	N	0.404276223	None	None	N
I/N	0.2654	likely_benign	0.2569	benign	-0.091	Destabilizing	0.283	N	0.612	neutral	None	None	None	None	N
I/P	0.7644	likely_pathogenic	0.6979	pathogenic	-0.521	Destabilizing	0.546	D	0.614	neutral	None	None	None	None	N
I/Q	0.3801	ambiguous	0.368	ambiguous	-0.305	Destabilizing	0.333	N	0.579	neutral	None	None	None	None	N
I/R	0.2981	likely_benign	0.2881	benign	0.183	Stabilizing	0.106	N	0.611	neutral	N	0.422515267	None	None	N
I/S	0.2706	likely_benign	0.2722	benign	-0.675	Destabilizing	0.011	N	0.429	neutral	None	None	None	None	N
I/T	0.1363	likely_benign	0.1529	benign	-0.632	Destabilizing	None	N	0.189	neutral	N	0.396128381	None	None	N
I/V	0.057	likely_benign	0.0564	benign	-0.521	Destabilizing	None	N	0.074	neutral	N	0.421475117	None	None	N
I/W	0.8079	likely_pathogenic	0.7801	pathogenic	-0.76	Destabilizing	0.871	D	0.577	neutral	None	None	None	None	N
I/Y	0.5301	ambiguous	0.5012	ambiguous	-0.493	Destabilizing	0.018	N	0.605	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.