TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33783	101572;101573;101574	chr2:178535268;178535267;178535266	chr2:179399995;179399994;179399993
N2AB	32142	96649;96650;96651	chr2:178535268;178535267;178535266	chr2:179399995;179399994;179399993
N2A	31215	93868;93869;93870	chr2:178535268;178535267;178535266	chr2:179399995;179399994;179399993
N2B	24718	74377;74378;74379	chr2:178535268;178535267;178535266	chr2:179399995;179399994;179399993
Novex-1	24843	74752;74753;74754	chr2:178535268;178535267;178535266	chr2:179399995;179399994;179399993
Novex-2	24910	74953;74954;74955	chr2:178535268;178535267;178535266	chr2:179399995;179399994;179399993
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-132
• Domain position: 95
• Structural Position: 131
• Q(SASA): 0.3896
• 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/R	None	None	0.972	N	0.621	0.211	0.303123707472	gnomAD-4.0.0	1.59107E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85785E-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
K/A	0.6189	likely_pathogenic	0.5659	pathogenic	-0.13	Destabilizing	0.996	D	0.747	deleterious	None	None	None	None	N
K/C	0.9164	likely_pathogenic	0.9062	pathogenic	-0.246	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
K/D	0.9047	likely_pathogenic	0.8793	pathogenic	0.283	Stabilizing	0.999	D	0.793	deleterious	None	None	None	None	N
K/E	0.4115	ambiguous	0.3688	ambiguous	0.301	Stabilizing	0.983	D	0.659	prob.neutral	N	0.451971382	None	None	N
K/F	0.9422	likely_pathogenic	0.9326	pathogenic	-0.301	Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	N
K/G	0.7607	likely_pathogenic	0.7317	pathogenic	-0.356	Destabilizing	0.999	D	0.694	prob.delet.	None	None	None	None	N
K/H	0.6719	likely_pathogenic	0.6485	pathogenic	-0.711	Destabilizing	0.999	D	0.702	prob.delet.	None	None	None	None	N
K/I	0.6218	likely_pathogenic	0.5854	pathogenic	0.391	Stabilizing	0.951	D	0.779	deleterious	N	0.452838174	None	None	N
K/L	0.6057	likely_pathogenic	0.5652	pathogenic	0.391	Stabilizing	0.963	D	0.694	prob.delet.	None	None	None	None	N
K/M	0.5122	ambiguous	0.4813	ambiguous	0.316	Stabilizing	0.997	D	0.696	prob.delet.	None	None	None	None	N
K/N	0.8229	likely_pathogenic	0.7737	pathogenic	0.207	Stabilizing	0.998	D	0.763	deleterious	N	0.453358249	None	None	N
K/P	0.8971	likely_pathogenic	0.8711	pathogenic	0.246	Stabilizing	0.999	D	0.764	deleterious	None	None	None	None	N
K/Q	0.2517	likely_benign	0.2327	benign	0.003	Stabilizing	0.988	D	0.791	deleterious	N	0.452838174	None	None	N
K/R	0.0958	likely_benign	0.0983	benign	-0.084	Destabilizing	0.972	D	0.621	neutral	N	0.452664815	None	None	N
K/S	0.7664	likely_pathogenic	0.7226	pathogenic	-0.396	Destabilizing	0.996	D	0.73	deleterious	None	None	None	None	N
K/T	0.4213	ambiguous	0.3909	ambiguous	-0.216	Destabilizing	0.995	D	0.751	deleterious	N	0.452838174	None	None	N
K/V	0.5259	ambiguous	0.4911	ambiguous	0.246	Stabilizing	0.971	D	0.764	deleterious	None	None	None	None	N
K/W	0.934	likely_pathogenic	0.9325	pathogenic	-0.242	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
K/Y	0.899	likely_pathogenic	0.8897	pathogenic	0.109	Stabilizing	0.994	D	0.769	deleterious	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.