TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31152	93679;93680;93681	chr2:178548172;178548171;178548170	chr2:179412899;179412898;179412897
N2AB	29511	88756;88757;88758	chr2:178548172;178548171;178548170	chr2:179412899;179412898;179412897
N2A	28584	85975;85976;85977	chr2:178548172;178548171;178548170	chr2:179412899;179412898;179412897
N2B	22087	66484;66485;66486	chr2:178548172;178548171;178548170	chr2:179412899;179412898;179412897
Novex-1	22212	66859;66860;66861	chr2:178548172;178548171;178548170	chr2:179412899;179412898;179412897
Novex-2	22279	67060;67061;67062	chr2:178548172;178548171;178548170	chr2:179412899;179412898;179412897
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Fn3-115
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.0988
• 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
M/R	None	None	0.912	N	0.637	0.257	0.510642626009	gnomAD-4.0.0	1.20041E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3126E-06	0	0
M/V	None	None	0.48	N	0.305	0.166	0.359763055319	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
M/A	0.4558	ambiguous	0.5337	ambiguous	-2.058	Highly Destabilizing	0.55	D	0.467	neutral	None	None	None	None	N
M/C	0.6698	likely_pathogenic	0.703	pathogenic	-2.017	Highly Destabilizing	0.993	D	0.673	neutral	None	None	None	None	N
M/D	0.9702	likely_pathogenic	0.9759	pathogenic	-1.896	Destabilizing	0.932	D	0.683	prob.neutral	None	None	None	None	N
M/E	0.7501	likely_pathogenic	0.7914	pathogenic	-1.635	Destabilizing	0.932	D	0.649	neutral	None	None	None	None	N
M/F	0.3324	likely_benign	0.3482	ambiguous	-0.697	Destabilizing	0.009	N	0.224	neutral	None	None	None	None	N
M/G	0.7284	likely_pathogenic	0.7552	pathogenic	-2.558	Highly Destabilizing	0.932	D	0.653	neutral	None	None	None	None	N
M/H	0.6814	likely_pathogenic	0.7175	pathogenic	-2.209	Highly Destabilizing	0.96	D	0.685	prob.neutral	None	None	None	None	N
M/I	0.4892	ambiguous	0.5689	pathogenic	-0.606	Destabilizing	0.679	D	0.437	neutral	N	0.438575223	None	None	N
M/K	0.2777	likely_benign	0.3538	ambiguous	-1.181	Destabilizing	0.837	D	0.59	neutral	N	0.401846419	None	None	N
M/L	0.1918	likely_benign	0.216	benign	-0.606	Destabilizing	0.166	N	0.342	neutral	N	0.435745562	None	None	N
M/N	0.7678	likely_pathogenic	0.8216	pathogenic	-1.679	Destabilizing	0.932	D	0.659	neutral	None	None	None	None	N
M/P	0.9944	likely_pathogenic	0.9954	pathogenic	-1.074	Destabilizing	0.977	D	0.698	prob.neutral	None	None	None	None	N
M/Q	0.3574	ambiguous	0.4131	ambiguous	-1.307	Destabilizing	0.977	D	0.586	neutral	None	None	None	None	N
M/R	0.3249	likely_benign	0.3905	ambiguous	-1.4	Destabilizing	0.912	D	0.637	neutral	N	0.415295719	None	None	N
M/S	0.5117	ambiguous	0.5863	pathogenic	-2.211	Highly Destabilizing	0.584	D	0.537	neutral	None	None	None	None	N
M/T	0.301	likely_benign	0.3708	ambiguous	-1.811	Destabilizing	0.028	N	0.377	neutral	N	0.466300542	None	None	N
M/V	0.1493	likely_benign	0.1736	benign	-1.074	Destabilizing	0.48	N	0.305	neutral	N	0.448405428	None	None	N
M/W	0.747	likely_pathogenic	0.7367	pathogenic	-1.031	Destabilizing	0.993	D	0.669	neutral	None	None	None	None	N
M/Y	0.5488	ambiguous	0.5553	ambiguous	-0.969	Destabilizing	0.013	N	0.377	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.