TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31129	93610;93611;93612	chr2:178548241;178548240;178548239	chr2:179412968;179412967;179412966
N2AB	29488	88687;88688;88689	chr2:178548241;178548240;178548239	chr2:179412968;179412967;179412966
N2A	28561	85906;85907;85908	chr2:178548241;178548240;178548239	chr2:179412968;179412967;179412966
N2B	22064	66415;66416;66417	chr2:178548241;178548240;178548239	chr2:179412968;179412967;179412966
Novex-1	22189	66790;66791;66792	chr2:178548241;178548240;178548239	chr2:179412968;179412967;179412966
Novex-2	22256	66991;66992;66993	chr2:178548241;178548240;178548239	chr2:179412968;179412967;179412966
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Fn3-115
• Domain position: 17
• Structural Position: 19
• Q(SASA): 0.1761
• 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
S/F	None	None	0.896	N	0.654	0.372	0.635364320139	gnomAD-4.0.0	2.73673E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59779E-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
S/A	0.1003	likely_benign	0.1148	benign	-0.66	Destabilizing	0.099	N	0.368	neutral	N	0.476304125	None	None	N
S/C	0.1177	likely_benign	0.1264	benign	-0.869	Destabilizing	0.009	N	0.353	neutral	N	0.483269566	None	None	N
S/D	0.659	likely_pathogenic	0.6472	pathogenic	-1.377	Destabilizing	0.617	D	0.521	neutral	None	None	None	None	N
S/E	0.6675	likely_pathogenic	0.6582	pathogenic	-1.356	Destabilizing	0.617	D	0.522	neutral	None	None	None	None	N
S/F	0.1994	likely_benign	0.23	benign	-1.131	Destabilizing	0.896	D	0.654	neutral	N	0.482193155	None	None	N
S/G	0.1467	likely_benign	0.1482	benign	-0.864	Destabilizing	0.617	D	0.475	neutral	None	None	None	None	N
S/H	0.3892	ambiguous	0.3895	ambiguous	-1.384	Destabilizing	0.992	D	0.587	neutral	None	None	None	None	N
S/I	0.3205	likely_benign	0.3711	ambiguous	-0.22	Destabilizing	0.85	D	0.63	neutral	None	None	None	None	N
S/K	0.7524	likely_pathogenic	0.7484	pathogenic	-0.573	Destabilizing	0.617	D	0.515	neutral	None	None	None	None	N
S/L	0.1443	likely_benign	0.1583	benign	-0.22	Destabilizing	0.447	N	0.533	neutral	None	None	None	None	N
S/M	0.2122	likely_benign	0.2409	benign	0.066	Stabilizing	0.92	D	0.599	neutral	None	None	None	None	N
S/N	0.2729	likely_benign	0.2926	benign	-0.848	Destabilizing	0.617	D	0.543	neutral	None	None	None	None	N
S/P	0.9683	likely_pathogenic	0.9656	pathogenic	-0.337	Destabilizing	0.896	D	0.631	neutral	N	0.520870427	None	None	N
S/Q	0.5809	likely_pathogenic	0.5807	pathogenic	-1.119	Destabilizing	0.92	D	0.573	neutral	None	None	None	None	N
S/R	0.6751	likely_pathogenic	0.6711	pathogenic	-0.41	Destabilizing	0.85	D	0.633	neutral	None	None	None	None	N
S/T	0.0749	likely_benign	0.0762	benign	-0.71	Destabilizing	0.001	N	0.137	neutral	N	0.451184735	None	None	N
S/V	0.2637	likely_benign	0.2966	benign	-0.337	Destabilizing	0.447	N	0.535	neutral	None	None	None	None	N
S/W	0.4124	ambiguous	0.4057	ambiguous	-1.176	Destabilizing	0.992	D	0.665	neutral	None	None	None	None	N
S/Y	0.22	likely_benign	0.2364	benign	-0.801	Destabilizing	0.963	D	0.647	neutral	N	0.47969794	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.