TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3013	9262;9263;9264	chr2:178768799;178768798;178768797	chr2:179633526;179633525;179633524
N2AB	3013	9262;9263;9264	chr2:178768799;178768798;178768797	chr2:179633526;179633525;179633524
N2A	3013	9262;9263;9264	chr2:178768799;178768798;178768797	chr2:179633526;179633525;179633524
N2B	2967	9124;9125;9126	chr2:178768799;178768798;178768797	chr2:179633526;179633525;179633524
Novex-1	2967	9124;9125;9126	chr2:178768799;178768798;178768797	chr2:179633526;179633525;179633524
Novex-2	2967	9124;9125;9126	chr2:178768799;178768798;178768797	chr2:179633526;179633525;179633524
Novex-3	3013	9262;9263;9264	chr2:178768799;178768798;178768797	chr2:179633526;179633525;179633524

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-20
• Domain position: 45
• Structural Position: 115
• Q(SASA): 0.1339
• 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
K/N	None	None	0.117	N	0.317	0.073	0.0762999501168	gnomAD-4.0.0	6.84088E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99295E-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
K/A	0.7807	likely_pathogenic	0.7627	pathogenic	-0.277	Destabilizing	0.067	N	0.315	neutral	None	None	None	None	N
K/C	0.7515	likely_pathogenic	0.7691	pathogenic	-0.102	Destabilizing	0.935	D	0.488	neutral	None	None	None	None	N
K/D	0.915	likely_pathogenic	0.907	pathogenic	-0.132	Destabilizing	0.149	N	0.392	neutral	None	None	None	None	N
K/E	0.7175	likely_pathogenic	0.7005	pathogenic	-0.063	Destabilizing	0.027	N	0.35	neutral	N	0.440023112	None	None	N
K/F	0.9206	likely_pathogenic	0.929	pathogenic	-0.095	Destabilizing	0.555	D	0.46	neutral	None	None	None	None	N
K/G	0.7808	likely_pathogenic	0.7363	pathogenic	-0.612	Destabilizing	0.149	N	0.379	neutral	None	None	None	None	N
K/H	0.3394	likely_benign	0.3631	ambiguous	-1.103	Destabilizing	0.555	D	0.359	neutral	None	None	None	None	N
K/I	0.6565	likely_pathogenic	0.6714	pathogenic	0.573	Stabilizing	0.555	D	0.475	neutral	None	None	None	None	N
K/L	0.675	likely_pathogenic	0.6756	pathogenic	0.573	Stabilizing	0.149	N	0.379	neutral	None	None	None	None	N
K/M	0.6279	likely_pathogenic	0.6248	pathogenic	0.544	Stabilizing	0.741	D	0.357	neutral	D	0.526922484	None	None	N
K/N	0.8125	likely_pathogenic	0.7856	pathogenic	-0.118	Destabilizing	0.117	N	0.317	neutral	N	0.453275918	None	None	N
K/P	0.9655	likely_pathogenic	0.9583	pathogenic	0.32	Stabilizing	0.555	D	0.403	neutral	None	None	None	None	N
K/Q	0.307	likely_benign	0.2969	benign	-0.23	Destabilizing	0.062	N	0.366	neutral	N	0.482501325	None	None	N
K/R	0.0575	likely_benign	0.0541	benign	-0.524	Destabilizing	None	N	0.085	neutral	N	0.394477353	None	None	N
K/S	0.8356	likely_pathogenic	0.8186	pathogenic	-0.65	Destabilizing	0.149	N	0.301	neutral	None	None	None	None	N
K/T	0.542	ambiguous	0.5167	ambiguous	-0.397	Destabilizing	0.117	N	0.329	neutral	N	0.446961558	None	None	N
K/V	0.6688	likely_pathogenic	0.6743	pathogenic	0.32	Stabilizing	0.149	N	0.428	neutral	None	None	None	None	N
K/W	0.7891	likely_pathogenic	0.8169	pathogenic	-0.042	Destabilizing	0.935	D	0.542	neutral	None	None	None	None	N
K/Y	0.7742	likely_pathogenic	0.8075	pathogenic	0.254	Stabilizing	0.555	D	0.403	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.