TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17704	53335;53336;53337	chr2:178607578;178607577;178607576	chr2:179472305;179472304;179472303
N2AB	16063	48412;48413;48414	chr2:178607578;178607577;178607576	chr2:179472305;179472304;179472303
N2A	15136	45631;45632;45633	chr2:178607578;178607577;178607576	chr2:179472305;179472304;179472303
N2B	8639	26140;26141;26142	chr2:178607578;178607577;178607576	chr2:179472305;179472304;179472303
Novex-1	8764	26515;26516;26517	chr2:178607578;178607577;178607576	chr2:179472305;179472304;179472303
Novex-2	8831	26716;26717;26718	chr2:178607578;178607577;178607576	chr2:179472305;179472304;179472303
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-113
• Domain position: 28
• Structural Position: 46
• Q(SASA): 0.2074
• Predicted PPI site: I

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	0.042	N	0.497	0.115	None	gnomAD-4.0.0	4.10637E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.39823E-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	0.2433	likely_benign	0.1748	benign	-0.682	Destabilizing	0.104	N	0.528	neutral	None	None	None	None	I
K/C	0.492	ambiguous	0.3867	ambiguous	-0.645	Destabilizing	0.958	D	0.777	deleterious	None	None	None	None	I
K/D	0.8082	likely_pathogenic	0.7611	pathogenic	-0.16	Destabilizing	0.22	N	0.614	neutral	None	None	None	None	I
K/E	0.2666	likely_benign	0.2052	benign	-0.04	Destabilizing	0.042	N	0.497	neutral	N	0.492268927	None	None	I
K/F	0.7612	likely_pathogenic	0.6451	pathogenic	-0.401	Destabilizing	0.22	N	0.749	deleterious	None	None	None	None	I
K/G	0.5673	likely_pathogenic	0.4655	ambiguous	-1.06	Destabilizing	0.22	N	0.659	neutral	None	None	None	None	I
K/H	0.443	ambiguous	0.3846	ambiguous	-1.466	Destabilizing	0.667	D	0.688	prob.neutral	None	None	None	None	I
K/I	0.1219	likely_benign	0.0754	benign	0.303	Stabilizing	None	N	0.466	neutral	N	0.317812031	None	None	I
K/L	0.2408	likely_benign	0.1733	benign	0.303	Stabilizing	None	N	0.439	neutral	None	None	None	None	I
K/M	0.128	likely_benign	0.0931	benign	0.259	Stabilizing	0.497	N	0.686	prob.neutral	None	None	None	None	I
K/N	0.5541	ambiguous	0.485	ambiguous	-0.478	Destabilizing	0.175	N	0.527	neutral	N	0.473683167	None	None	I
K/P	0.6993	likely_pathogenic	0.6593	pathogenic	0.005	Stabilizing	0.667	D	0.669	neutral	None	None	None	None	I
K/Q	0.178	likely_benign	0.1405	benign	-0.554	Destabilizing	0.175	N	0.533	neutral	N	0.492268927	None	None	I
K/R	0.0993	likely_benign	0.0801	benign	-0.636	Destabilizing	None	N	0.213	neutral	N	0.492268927	None	None	I
K/S	0.4562	ambiguous	0.3653	ambiguous	-1.178	Destabilizing	0.104	N	0.501	neutral	None	None	None	None	I
K/T	0.1072	likely_benign	0.0795	benign	-0.842	Destabilizing	0.081	N	0.56	neutral	N	0.43589557	None	None	I
K/V	0.1228	likely_benign	0.0809	benign	0.005	Stabilizing	0.025	N	0.558	neutral	None	None	None	None	I
K/W	0.8192	likely_pathogenic	0.7361	pathogenic	-0.258	Destabilizing	0.958	D	0.769	deleterious	None	None	None	None	I
K/Y	0.6196	likely_pathogenic	0.5506	ambiguous	0.049	Stabilizing	0.859	D	0.739	prob.delet.	None	None	None	None	I

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.