TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27590	82993;82994;82995	chr2:178563364;178563363;178563362	chr2:179428091;179428090;179428089
N2AB	25949	78070;78071;78072	chr2:178563364;178563363;178563362	chr2:179428091;179428090;179428089
N2A	25022	75289;75290;75291	chr2:178563364;178563363;178563362	chr2:179428091;179428090;179428089
N2B	18525	55798;55799;55800	chr2:178563364;178563363;178563362	chr2:179428091;179428090;179428089
Novex-1	18650	56173;56174;56175	chr2:178563364;178563363;178563362	chr2:179428091;179428090;179428089
Novex-2	18717	56374;56375;56376	chr2:178563364;178563363;178563362	chr2:179428091;179428090;179428089
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-89
• Domain position: 21
• Structural Position: 23
• Q(SASA): 0.0938
• 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
A/P	None	None	0.896	N	0.719	0.329	0.462721901306	gnomAD-4.0.0	6.84278E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99515E-07	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
A/C	0.3551	ambiguous	0.3517	ambiguous	-1.184	Destabilizing	0.977	D	0.624	neutral	None	None	None	None	N
A/D	0.4955	ambiguous	0.4225	ambiguous	-2.433	Highly Destabilizing	0.617	D	0.701	prob.neutral	None	None	None	None	N
A/E	0.3468	ambiguous	0.2882	benign	-2.235	Highly Destabilizing	0.379	N	0.689	prob.neutral	N	0.477458899	None	None	N
A/F	0.2782	likely_benign	0.2685	benign	-0.685	Destabilizing	0.85	D	0.715	prob.delet.	None	None	None	None	N
A/G	0.1337	likely_benign	0.1281	benign	-1.513	Destabilizing	0.334	N	0.522	neutral	N	0.511515544	None	None	N
A/H	0.4666	ambiguous	0.4192	ambiguous	-2.068	Highly Destabilizing	0.977	D	0.675	prob.neutral	None	None	None	None	N
A/I	0.225	likely_benign	0.2115	benign	0.238	Stabilizing	0.217	N	0.712	prob.delet.	None	None	None	None	N
A/K	0.6231	likely_pathogenic	0.5229	ambiguous	-1.217	Destabilizing	0.447	N	0.691	prob.neutral	None	None	None	None	N
A/L	0.1587	likely_benign	0.1484	benign	0.238	Stabilizing	0.447	N	0.64	neutral	None	None	None	None	N
A/M	0.1924	likely_benign	0.1838	benign	-0.082	Destabilizing	0.85	D	0.665	neutral	None	None	None	None	N
A/N	0.2686	likely_benign	0.2506	benign	-1.526	Destabilizing	0.85	D	0.701	prob.neutral	None	None	None	None	N
A/P	0.9553	likely_pathogenic	0.9421	pathogenic	-0.143	Destabilizing	0.896	D	0.719	prob.delet.	N	0.49467728	None	None	N
A/Q	0.3355	likely_benign	0.2885	benign	-1.32	Destabilizing	0.048	N	0.547	neutral	None	None	None	None	N
A/R	0.5506	ambiguous	0.4571	ambiguous	-1.338	Destabilizing	0.739	D	0.718	prob.delet.	None	None	None	None	N
A/S	0.0781	likely_benign	0.0777	benign	-1.904	Destabilizing	0.02	N	0.223	neutral	N	0.393106719	None	None	N
A/T	0.0816	likely_benign	0.0793	benign	-1.582	Destabilizing	0.016	N	0.446	neutral	N	0.421085541	None	None	N
A/V	0.1378	likely_benign	0.1288	benign	-0.143	Destabilizing	0.004	N	0.453	neutral	N	0.50934203	None	None	N
A/W	0.7494	likely_pathogenic	0.7123	pathogenic	-1.521	Destabilizing	0.992	D	0.721	prob.delet.	None	None	None	None	N
A/Y	0.4293	ambiguous	0.4099	ambiguous	-0.932	Destabilizing	0.92	D	0.715	prob.delet.	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.