TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9512	28759;28760;28761	chr2:178709785;178709784;178709783	chr2:179574512;179574511;179574510
N2AB	9195	27808;27809;27810	chr2:178709785;178709784;178709783	chr2:179574512;179574511;179574510
N2A	8268	25027;25028;25029	chr2:178709785;178709784;178709783	chr2:179574512;179574511;179574510
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-81
• Domain position: 20
• Structural Position: 29
• Q(SASA): 0.405
• 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	0.201	None	0.603	0.144	0.171388866994	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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	0.3462	ambiguous	0.2589	benign	-0.248	Destabilizing	0.399	N	0.578	neutral	None	None	None	None	N
K/C	0.5443	ambiguous	0.4685	ambiguous	-0.563	Destabilizing	0.982	D	0.677	prob.neutral	None	None	None	None	N
K/D	0.7148	likely_pathogenic	0.6083	pathogenic	-0.003	Destabilizing	0.002	N	0.441	neutral	None	None	None	None	N
K/E	0.2223	likely_benign	0.1731	benign	0.092	Stabilizing	0.201	N	0.603	neutral	None	None	None	None	N
K/F	0.6083	likely_pathogenic	0.5	ambiguous	-0.007	Destabilizing	0.826	D	0.692	prob.neutral	None	None	None	None	N
K/G	0.5441	ambiguous	0.3983	ambiguous	-0.572	Destabilizing	0.399	N	0.609	neutral	None	None	None	None	N
K/H	0.2168	likely_benign	0.1856	benign	-0.754	Destabilizing	0.947	D	0.672	neutral	None	None	None	None	N
K/I	0.202	likely_benign	0.1653	benign	0.565	Stabilizing	0.781	D	0.707	prob.neutral	None	None	None	None	N
K/L	0.2391	likely_benign	0.188	benign	0.565	Stabilizing	0.7	D	0.641	neutral	None	None	None	None	N
K/M	0.165	likely_benign	0.1434	benign	0.141	Stabilizing	0.982	D	0.662	neutral	None	None	None	None	N
K/N	0.457	ambiguous	0.3485	ambiguous	-0.363	Destabilizing	0.638	D	0.612	neutral	None	None	None	None	N
K/P	0.9131	likely_pathogenic	0.8361	pathogenic	0.324	Stabilizing	0.826	D	0.701	prob.neutral	None	None	None	None	N
K/Q	0.1055	likely_benign	0.0917	benign	-0.385	Destabilizing	0.468	N	0.645	neutral	None	None	None	None	N
K/R	0.0704	likely_benign	0.0662	benign	-0.421	Destabilizing	0.004	N	0.437	neutral	None	None	None	None	N
K/S	0.3706	ambiguous	0.2735	benign	-0.909	Destabilizing	0.399	N	0.582	neutral	None	None	None	None	N
K/T	0.1191	likely_benign	0.1004	benign	-0.621	Destabilizing	0.638	D	0.665	neutral	None	None	None	None	N
K/V	0.2163	likely_benign	0.1753	benign	0.324	Stabilizing	0.7	D	0.687	prob.neutral	None	None	None	None	N
K/W	0.615	likely_pathogenic	0.4946	ambiguous	0.033	Stabilizing	0.982	D	0.643	neutral	None	None	None	None	N
K/Y	0.505	ambiguous	0.4046	ambiguous	0.333	Stabilizing	0.826	D	0.691	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.