TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33768	101527;101528;101529	chr2:178535313;178535312;178535311	chr2:179400040;179400039;179400038
N2AB	32127	96604;96605;96606	chr2:178535313;178535312;178535311	chr2:179400040;179400039;179400038
N2A	31200	93823;93824;93825	chr2:178535313;178535312;178535311	chr2:179400040;179400039;179400038
N2B	24703	74332;74333;74334	chr2:178535313;178535312;178535311	chr2:179400040;179400039;179400038
Novex-1	24828	74707;74708;74709	chr2:178535313;178535312;178535311	chr2:179400040;179400039;179400038
Novex-2	24895	74908;74909;74910	chr2:178535313;178535312;178535311	chr2:179400040;179400039;179400038
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Fn3-132
• Domain position: 80
• Structural Position: 114
• Q(SASA): 0.1808
• 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
F/S	None	None	1.0	N	0.665	0.515	0.601658297244	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
F/A	0.9666	likely_pathogenic	0.9632	pathogenic	-0.752	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	N
F/C	0.8983	likely_pathogenic	0.8989	pathogenic	-0.351	Destabilizing	1.0	D	0.714	prob.delet.	N	0.452005881	None	None	N
F/D	0.9927	likely_pathogenic	0.9926	pathogenic	0.961	Stabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
F/E	0.9923	likely_pathogenic	0.9928	pathogenic	0.936	Stabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
F/G	0.9894	likely_pathogenic	0.9887	pathogenic	-0.919	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
F/H	0.8959	likely_pathogenic	0.9206	pathogenic	0.339	Stabilizing	1.0	D	0.643	neutral	None	None	None	None	N
F/I	0.857	likely_pathogenic	0.8638	pathogenic	-0.342	Destabilizing	0.989	D	0.567	neutral	N	0.400152908	None	None	N
F/K	0.9905	likely_pathogenic	0.9918	pathogenic	0.018	Stabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
F/L	0.9885	likely_pathogenic	0.9881	pathogenic	-0.342	Destabilizing	0.352	N	0.355	neutral	N	0.441519528	None	None	N
F/M	0.9423	likely_pathogenic	0.943	pathogenic	-0.34	Destabilizing	0.987	D	0.609	neutral	None	None	None	None	N
F/N	0.9584	likely_pathogenic	0.9617	pathogenic	0.043	Stabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
F/P	0.9995	likely_pathogenic	0.9994	pathogenic	-0.459	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
F/Q	0.9841	likely_pathogenic	0.9861	pathogenic	0.023	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
F/R	0.9731	likely_pathogenic	0.9754	pathogenic	0.393	Stabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
F/S	0.9615	likely_pathogenic	0.9651	pathogenic	-0.633	Destabilizing	1.0	D	0.665	neutral	N	0.467396621	None	None	N
F/T	0.9713	likely_pathogenic	0.9712	pathogenic	-0.566	Destabilizing	1.0	D	0.632	neutral	None	None	None	None	N
F/V	0.851	likely_pathogenic	0.8598	pathogenic	-0.459	Destabilizing	0.984	D	0.637	neutral	N	0.377294691	None	None	N
F/W	0.747	likely_pathogenic	0.7931	pathogenic	-0.199	Destabilizing	1.0	D	0.607	neutral	None	None	None	None	N
F/Y	0.2343	likely_benign	0.278	benign	-0.166	Destabilizing	0.998	D	0.561	neutral	N	0.398326111	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.