TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7362	22309;22310;22311	chr2:178722815;178722814;178722813	chr2:179587542;179587541;179587540
N2AB	7045	21358;21359;21360	chr2:178722815;178722814;178722813	chr2:179587542;179587541;179587540
N2A	6118	18577;18578;18579	chr2:178722815;178722814;178722813	chr2:179587542;179587541;179587540
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: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-58
• Domain position: 40
• Structural Position: 56
• Q(SASA): 0.4511
• 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/E	None	None	0.998	N	0.529	0.299	0.391313282164	gnomAD-4.0.0	1.59219E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85964E-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	0.5766	likely_pathogenic	0.7258	pathogenic	-0.341	Destabilizing	0.999	D	0.604	neutral	None	None	None	None	N
K/C	0.8655	likely_pathogenic	0.9134	pathogenic	-0.518	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
K/D	0.9087	likely_pathogenic	0.957	pathogenic	0.205	Stabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
K/E	0.418	ambiguous	0.5884	pathogenic	0.297	Stabilizing	0.998	D	0.529	neutral	N	0.433914057	None	None	N
K/F	0.896	likely_pathogenic	0.9482	pathogenic	-0.161	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
K/G	0.7896	likely_pathogenic	0.9001	pathogenic	-0.644	Destabilizing	0.999	D	0.631	neutral	None	None	None	None	N
K/H	0.5574	ambiguous	0.658	pathogenic	-0.748	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
K/I	0.4811	ambiguous	0.6046	pathogenic	0.416	Stabilizing	0.993	D	0.718	prob.delet.	N	0.498909685	None	None	N
K/L	0.4686	ambiguous	0.5803	pathogenic	0.416	Stabilizing	0.982	D	0.631	neutral	None	None	None	None	N
K/M	0.3764	ambiguous	0.4896	ambiguous	0.005	Stabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
K/N	0.8206	likely_pathogenic	0.9058	pathogenic	-0.227	Destabilizing	1.0	D	0.679	prob.neutral	N	0.48242008	None	None	N
K/P	0.6525	likely_pathogenic	0.7666	pathogenic	0.193	Stabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
K/Q	0.2579	likely_benign	0.3464	ambiguous	-0.248	Destabilizing	0.998	D	0.674	neutral	N	0.475262034	None	None	N
K/R	0.09	likely_benign	0.101	benign	-0.242	Destabilizing	0.996	D	0.489	neutral	N	0.495984023	None	None	N
K/S	0.7623	likely_pathogenic	0.8737	pathogenic	-0.817	Destabilizing	0.999	D	0.612	neutral	None	None	None	None	N
K/T	0.4674	ambiguous	0.6139	pathogenic	-0.534	Destabilizing	0.999	D	0.677	prob.neutral	N	0.493559793	None	None	N
K/V	0.433	ambiguous	0.5376	ambiguous	0.193	Stabilizing	0.996	D	0.64	neutral	None	None	None	None	N
K/W	0.8852	likely_pathogenic	0.9365	pathogenic	-0.114	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
K/Y	0.8132	likely_pathogenic	0.8845	pathogenic	0.187	Stabilizing	0.997	D	0.701	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.