TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22019	66280;66281;66282	chr2:178582401;178582400;178582399	chr2:179447128;179447127;179447126
N2AB	20378	61357;61358;61359	chr2:178582401;178582400;178582399	chr2:179447128;179447127;179447126
N2A	19451	58576;58577;58578	chr2:178582401;178582400;178582399	chr2:179447128;179447127;179447126
N2B	12954	39085;39086;39087	chr2:178582401;178582400;178582399	chr2:179447128;179447127;179447126
Novex-1	13079	39460;39461;39462	chr2:178582401;178582400;178582399	chr2:179447128;179447127;179447126
Novex-2	13146	39661;39662;39663	chr2:178582401;178582400;178582399	chr2:179447128;179447127;179447126
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: Fn3-47
• Domain position: 64
• Structural Position: 96
• Q(SASA): 0.7984
• 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/I	rs1164328228	None	0.97	N	0.61	0.366	0.48748946032	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	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	0.88	likely_pathogenic	0.884	pathogenic	0.065	Stabilizing	0.86	D	0.457	neutral	None	None	None	None	N
K/C	0.9376	likely_pathogenic	0.9157	pathogenic	-0.276	Destabilizing	0.998	D	0.664	neutral	None	None	None	None	N
K/D	0.8868	likely_pathogenic	0.8909	pathogenic	-0.202	Destabilizing	0.978	D	0.469	neutral	None	None	None	None	N
K/E	0.8132	likely_pathogenic	0.8276	pathogenic	-0.202	Destabilizing	0.822	D	0.469	neutral	N	0.496084732	None	None	N
K/F	0.972	likely_pathogenic	0.9745	pathogenic	-0.165	Destabilizing	0.993	D	0.607	neutral	None	None	None	None	N
K/G	0.7824	likely_pathogenic	0.7352	pathogenic	-0.104	Destabilizing	0.019	N	0.317	neutral	None	None	None	None	N
K/H	0.538	ambiguous	0.5092	ambiguous	-0.226	Destabilizing	0.994	D	0.499	neutral	None	None	None	None	N
K/I	0.9373	likely_pathogenic	0.9472	pathogenic	0.434	Stabilizing	0.97	D	0.61	neutral	N	0.500869025	None	None	N
K/L	0.8553	likely_pathogenic	0.8694	pathogenic	0.434	Stabilizing	0.956	D	0.427	neutral	None	None	None	None	N
K/M	0.7654	likely_pathogenic	0.7833	pathogenic	0.054	Stabilizing	0.998	D	0.503	neutral	None	None	None	None	N
K/N	0.7516	likely_pathogenic	0.7545	pathogenic	0.161	Stabilizing	0.942	D	0.457	neutral	N	0.4732638	None	None	N
K/P	0.9676	likely_pathogenic	0.9656	pathogenic	0.337	Stabilizing	0.993	D	0.496	neutral	None	None	None	None	N
K/Q	0.5103	ambiguous	0.5025	ambiguous	0.007	Stabilizing	0.942	D	0.52	neutral	N	0.484459837	None	None	N
K/R	0.1282	likely_benign	0.1179	benign	-0.011	Destabilizing	0.014	N	0.125	neutral	N	0.461396155	None	None	N
K/S	0.8868	likely_pathogenic	0.8894	pathogenic	-0.226	Destabilizing	0.86	D	0.453	neutral	None	None	None	None	N
K/T	0.7723	likely_pathogenic	0.7915	pathogenic	-0.097	Destabilizing	0.942	D	0.447	neutral	N	0.484966816	None	None	N
K/V	0.9088	likely_pathogenic	0.9195	pathogenic	0.337	Stabilizing	0.978	D	0.511	neutral	None	None	None	None	N
K/W	0.9518	likely_pathogenic	0.9514	pathogenic	-0.239	Destabilizing	0.998	D	0.691	prob.neutral	None	None	None	None	N
K/Y	0.8783	likely_pathogenic	0.8736	pathogenic	0.108	Stabilizing	0.993	D	0.559	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.