TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29616	89071;89072;89073	chr2:178554501;178554500;178554499	chr2:179419228;179419227;179419226
N2AB	27975	84148;84149;84150	chr2:178554501;178554500;178554499	chr2:179419228;179419227;179419226
N2A	27048	81367;81368;81369	chr2:178554501;178554500;178554499	chr2:179419228;179419227;179419226
N2B	20551	61876;61877;61878	chr2:178554501;178554500;178554499	chr2:179419228;179419227;179419226
Novex-1	20676	62251;62252;62253	chr2:178554501;178554500;178554499	chr2:179419228;179419227;179419226
Novex-2	20743	62452;62453;62454	chr2:178554501;178554500;178554499	chr2:179419228;179419227;179419226
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-103
• Domain position: 84
• Structural Position: 117
• Q(SASA): 0.522
• 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/F	rs768798726	None	0.317	N	0.584	0.105	None	gnomAD-4.0.0	1.59433E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88872E-05	0	0	0	0
I/N	None	None	0.484	N	0.653	0.339	0.666472316455	gnomAD-4.0.0	1.59284E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85915E-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	0.1151	likely_benign	0.1152	benign	-1.509	Destabilizing	0.001	N	0.319	neutral	None	None	None	None	N
I/C	0.4875	ambiguous	0.4985	ambiguous	-1.011	Destabilizing	0.824	D	0.581	neutral	None	None	None	None	N
I/D	0.4829	ambiguous	0.489	ambiguous	-0.675	Destabilizing	0.555	D	0.652	neutral	None	None	None	None	N
I/E	0.3907	ambiguous	0.3819	ambiguous	-0.687	Destabilizing	0.555	D	0.63	neutral	None	None	None	None	N
I/F	0.1443	likely_benign	0.1549	benign	-1.04	Destabilizing	0.317	N	0.584	neutral	N	0.510803468	None	None	N
I/G	0.4547	ambiguous	0.4687	ambiguous	-1.808	Destabilizing	0.081	N	0.627	neutral	None	None	None	None	N
I/H	0.414	ambiguous	0.442	ambiguous	-0.851	Destabilizing	0.935	D	0.646	neutral	None	None	None	None	N
I/K	0.3313	likely_benign	0.3431	ambiguous	-0.903	Destabilizing	0.38	N	0.634	neutral	None	None	None	None	N
I/L	0.1104	likely_benign	0.1118	benign	-0.778	Destabilizing	0.012	N	0.239	neutral	N	0.455526188	None	None	N
I/M	0.0949	likely_benign	0.0961	benign	-0.688	Destabilizing	0.317	N	0.596	neutral	N	0.462204231	None	None	N
I/N	0.2266	likely_benign	0.2302	benign	-0.711	Destabilizing	0.484	N	0.653	neutral	N	0.509763318	None	None	N
I/P	0.2986	likely_benign	0.3083	benign	-0.989	Destabilizing	0.555	D	0.653	neutral	None	None	None	None	N
I/Q	0.3487	ambiguous	0.3628	ambiguous	-0.91	Destabilizing	0.555	D	0.653	neutral	None	None	None	None	N
I/R	0.2424	likely_benign	0.2662	benign	-0.28	Destabilizing	0.555	D	0.653	neutral	None	None	None	None	N
I/S	0.1556	likely_benign	0.1612	benign	-1.365	Destabilizing	0.062	N	0.584	neutral	N	0.47822969	None	None	N
I/T	0.0667	likely_benign	0.0713	benign	-1.257	Destabilizing	0.062	N	0.487	neutral	N	0.461529441	None	None	N
I/V	0.0594	likely_benign	0.0601	benign	-0.989	Destabilizing	None	N	0.197	neutral	N	0.415469077	None	None	N
I/W	0.6902	likely_pathogenic	0.7292	pathogenic	-1.02	Destabilizing	0.935	D	0.689	prob.neutral	None	None	None	None	N
I/Y	0.4535	ambiguous	0.4755	ambiguous	-0.818	Destabilizing	0.555	D	0.601	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.