TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4986	15181;15182;15183	chr2:178734968;178734967;178734966	chr2:179599695;179599694;179599693
N2AB	4669	14230;14231;14232	chr2:178734968;178734967;178734966	chr2:179599695;179599694;179599693
N2A	3742	11449;11450;11451	chr2:178734968;178734967;178734966	chr2:179599695;179599694;179599693
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-33
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.5897
• 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	0.999	N	0.729	0.283	0.151104730317	gnomAD-4.0.0	6.94833E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.19443E-05	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	0.6688	likely_pathogenic	0.7144	pathogenic	-0.715	Destabilizing	0.994	D	0.64	neutral	None	None	None	None	N
K/C	0.9402	likely_pathogenic	0.9494	pathogenic	-0.656	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
K/D	0.8317	likely_pathogenic	0.8575	pathogenic	0.297	Stabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	N
K/E	0.4804	ambiguous	0.5121	ambiguous	0.398	Stabilizing	0.992	D	0.621	neutral	N	0.444787643	None	None	N
K/F	0.9428	likely_pathogenic	0.9517	pathogenic	-0.5	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
K/G	0.7478	likely_pathogenic	0.7772	pathogenic	-1.052	Destabilizing	0.999	D	0.623	neutral	None	None	None	None	N
K/H	0.5993	likely_pathogenic	0.6283	pathogenic	-1.327	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	N
K/I	0.7661	likely_pathogenic	0.7844	pathogenic	0.148	Stabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
K/L	0.7013	likely_pathogenic	0.7167	pathogenic	0.148	Stabilizing	0.998	D	0.623	neutral	None	None	None	None	N
K/M	0.4977	ambiguous	0.5159	ambiguous	0.057	Stabilizing	1.0	D	0.717	prob.delet.	D	0.591110056	None	None	N
K/N	0.7345	likely_pathogenic	0.7498	pathogenic	-0.232	Destabilizing	0.999	D	0.729	prob.delet.	N	0.501896061	None	None	N
K/P	0.6798	likely_pathogenic	0.7109	pathogenic	-0.11	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
K/Q	0.3042	likely_benign	0.3221	benign	-0.349	Destabilizing	0.998	D	0.717	prob.delet.	N	0.473975897	None	None	N
K/R	0.1086	likely_benign	0.1106	benign	-0.399	Destabilizing	0.467	N	0.278	neutral	N	0.45321752	None	None	N
K/S	0.7747	likely_pathogenic	0.8019	pathogenic	-1.027	Destabilizing	0.997	D	0.677	prob.neutral	None	None	None	None	N
K/T	0.497	ambiguous	0.5483	ambiguous	-0.719	Destabilizing	0.999	D	0.717	prob.delet.	N	0.443713565	None	None	N
K/V	0.7096	likely_pathogenic	0.7354	pathogenic	-0.11	Destabilizing	0.999	D	0.696	prob.neutral	None	None	None	None	N
K/W	0.9272	likely_pathogenic	0.9336	pathogenic	-0.301	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
K/Y	0.8593	likely_pathogenic	0.8723	pathogenic	-0.015	Destabilizing	1.0	D	0.692	prob.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.