TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9529	28810;28811;28812	chr2:178709734;178709733;178709732	chr2:179574461;179574460;179574459
N2AB	9212	27859;27860;27861	chr2:178709734;178709733;178709732	chr2:179574461;179574460;179574459
N2A	8285	25078;25079;25080	chr2:178709734;178709733;178709732	chr2:179574461;179574460;179574459
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: 37
• Structural Position: 50
• Q(SASA): 0.197
• 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	rs876658049	None	0.638	None	0.499	0.26	0.128392430309	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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	0.9084	likely_pathogenic	0.8968	pathogenic	-0.975	Destabilizing	0.399	N	0.523	neutral	None	None	None	None	N
K/C	0.8432	likely_pathogenic	0.8374	pathogenic	-0.948	Destabilizing	0.982	D	0.744	deleterious	None	None	None	None	N
K/D	0.9876	likely_pathogenic	0.9876	pathogenic	-0.299	Destabilizing	0.7	D	0.591	neutral	None	None	None	None	N
K/E	0.7271	likely_pathogenic	0.7433	pathogenic	-0.147	Destabilizing	0.201	N	0.531	neutral	None	None	None	None	N
K/F	0.9383	likely_pathogenic	0.943	pathogenic	-0.696	Destabilizing	0.7	D	0.745	deleterious	None	None	None	None	N
K/G	0.9526	likely_pathogenic	0.9507	pathogenic	-1.367	Destabilizing	0.7	D	0.615	neutral	None	None	None	None	N
K/H	0.5871	likely_pathogenic	0.637	pathogenic	-1.755	Destabilizing	0.947	D	0.632	neutral	None	None	None	None	N
K/I	0.7282	likely_pathogenic	0.6743	pathogenic	0.064	Stabilizing	0.468	N	0.704	prob.neutral	None	None	None	None	N
K/L	0.6257	likely_pathogenic	0.6157	pathogenic	0.064	Stabilizing	0.002	N	0.49	neutral	None	None	None	None	N
K/M	0.5438	ambiguous	0.5604	ambiguous	0.003	Stabilizing	0.7	D	0.64	neutral	None	None	None	None	N
K/N	0.9276	likely_pathogenic	0.9324	pathogenic	-0.72	Destabilizing	0.638	D	0.499	neutral	None	None	None	None	N
K/P	0.9971	likely_pathogenic	0.9957	pathogenic	-0.254	Destabilizing	0.826	D	0.597	neutral	None	None	None	None	N
K/Q	0.3153	likely_benign	0.3534	ambiguous	-0.744	Destabilizing	0.638	D	0.505	neutral	None	None	None	None	N
K/R	0.0887	likely_benign	0.081	benign	-0.725	Destabilizing	0.004	N	0.386	neutral	None	None	None	None	N
K/S	0.9376	likely_pathogenic	0.9394	pathogenic	-1.469	Destabilizing	0.399	N	0.531	neutral	None	None	None	None	N
K/T	0.8416	likely_pathogenic	0.8247	pathogenic	-1.088	Destabilizing	0.638	D	0.572	neutral	None	None	None	None	N
K/V	0.7401	likely_pathogenic	0.6774	pathogenic	-0.254	Destabilizing	0.25	N	0.614	neutral	None	None	None	None	N
K/W	0.9088	likely_pathogenic	0.909	pathogenic	-0.542	Destabilizing	0.982	D	0.728	prob.delet.	None	None	None	None	N
K/Y	0.8507	likely_pathogenic	0.8715	pathogenic	-0.221	Destabilizing	0.826	D	0.685	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.