TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25268	76027;76028;76029	chr2:178570330;178570329;178570328	chr2:179435057;179435056;179435055
N2AB	23627	71104;71105;71106	chr2:178570330;178570329;178570328	chr2:179435057;179435056;179435055
N2A	22700	68323;68324;68325	chr2:178570330;178570329;178570328	chr2:179435057;179435056;179435055
N2B	16203	48832;48833;48834	chr2:178570330;178570329;178570328	chr2:179435057;179435056;179435055
Novex-1	16328	49207;49208;49209	chr2:178570330;178570329;178570328	chr2:179435057;179435056;179435055
Novex-2	16395	49408;49409;49410	chr2:178570330;178570329;178570328	chr2:179435057;179435056;179435055
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-71
• Domain position: 65
• Structural Position: 96
• Q(SASA): 0.8825
• 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	rs1324895308	0.318	0.967	N	0.648	0.252	0.180583059064	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	2.91E-05	None	0	0	None	0	None	0	0	0
K/N	rs1324895308	0.318	0.967	N	0.648	0.252	0.180583059064	gnomAD-4.0.0	1.59236E-06	None	None	None	None	N	None	0	2.28822E-05	None	0	0	None	0	0	0	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	0.8318	likely_pathogenic	0.8868	pathogenic	0.081	Stabilizing	0.916	D	0.553	neutral	None	None	None	None	N
K/C	0.8965	likely_pathogenic	0.9373	pathogenic	-0.296	Destabilizing	0.999	D	0.703	prob.neutral	None	None	None	None	N
K/D	0.9056	likely_pathogenic	0.9285	pathogenic	-0.11	Destabilizing	0.987	D	0.627	neutral	None	None	None	None	N
K/E	0.8071	likely_pathogenic	0.8629	pathogenic	-0.111	Destabilizing	0.892	D	0.541	neutral	N	0.502757201	None	None	N
K/F	0.9779	likely_pathogenic	0.9872	pathogenic	-0.163	Destabilizing	0.999	D	0.665	neutral	None	None	None	None	N
K/G	0.7016	likely_pathogenic	0.774	pathogenic	-0.086	Destabilizing	0.975	D	0.562	neutral	None	None	None	None	N
K/H	0.4825	ambiguous	0.5738	pathogenic	-0.202	Destabilizing	0.997	D	0.607	neutral	None	None	None	None	N
K/I	0.951	likely_pathogenic	0.9692	pathogenic	0.44	Stabilizing	0.987	D	0.681	prob.neutral	None	None	None	None	N
K/L	0.8622	likely_pathogenic	0.906	pathogenic	0.44	Stabilizing	0.975	D	0.562	neutral	None	None	None	None	N
K/M	0.8265	likely_pathogenic	0.8801	pathogenic	0.074	Stabilizing	0.999	D	0.604	neutral	N	0.514321563	None	None	N
K/N	0.8077	likely_pathogenic	0.8539	pathogenic	0.16	Stabilizing	0.967	D	0.648	neutral	N	0.461561152	None	None	N
K/P	0.9534	likely_pathogenic	0.9738	pathogenic	0.346	Stabilizing	0.996	D	0.617	neutral	None	None	None	None	N
K/Q	0.4471	ambiguous	0.55	ambiguous	0.01	Stabilizing	0.967	D	0.659	neutral	N	0.49494986	None	None	N
K/R	0.0871	likely_benign	0.0992	benign	0.001	Stabilizing	0.025	N	0.18	neutral	N	0.469164702	None	None	N
K/S	0.8239	likely_pathogenic	0.8782	pathogenic	-0.251	Destabilizing	0.916	D	0.607	neutral	None	None	None	None	N
K/T	0.7665	likely_pathogenic	0.8445	pathogenic	-0.12	Destabilizing	0.967	D	0.611	neutral	N	0.479074105	None	None	N
K/V	0.8976	likely_pathogenic	0.9339	pathogenic	0.346	Stabilizing	0.987	D	0.628	neutral	None	None	None	None	N
K/W	0.9436	likely_pathogenic	0.9684	pathogenic	-0.236	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
K/Y	0.9079	likely_pathogenic	0.9354	pathogenic	0.118	Stabilizing	0.996	D	0.641	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.