TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25657	77194;77195;77196	chr2:178569163;178569162;178569161	chr2:179433890;179433889;179433888
N2AB	24016	72271;72272;72273	chr2:178569163;178569162;178569161	chr2:179433890;179433889;179433888
N2A	23089	69490;69491;69492	chr2:178569163;178569162;178569161	chr2:179433890;179433889;179433888
N2B	16592	49999;50000;50001	chr2:178569163;178569162;178569161	chr2:179433890;179433889;179433888
Novex-1	16717	50374;50375;50376	chr2:178569163;178569162;178569161	chr2:179433890;179433889;179433888
Novex-2	16784	50575;50576;50577	chr2:178569163;178569162;178569161	chr2:179433890;179433889;179433888
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: Fn3-74
• Domain position: 57
• Structural Position: 88
• Q(SASA): 0.4046
• 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/Q	None	None	0.897	N	0.531	0.197	0.1749357433	gnomAD-4.0.0	1.59245E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86031E-06	0	0
K/T	None	None	0.978	N	0.552	0.287	0.309530620856	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.21507E-04	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	0.6267	likely_pathogenic	0.6903	pathogenic	-0.185	Destabilizing	0.931	D	0.495	neutral	None	None	None	None	N
K/C	0.7928	likely_pathogenic	0.8361	pathogenic	-0.367	Destabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	N
K/D	0.8104	likely_pathogenic	0.8551	pathogenic	0.059	Stabilizing	0.99	D	0.563	neutral	None	None	None	None	N
K/E	0.4471	ambiguous	0.537	ambiguous	0.128	Stabilizing	0.86	D	0.479	neutral	N	0.494852581	None	None	N
K/F	0.9314	likely_pathogenic	0.9543	pathogenic	-0.145	Destabilizing	0.996	D	0.647	neutral	None	None	None	None	N
K/G	0.64	likely_pathogenic	0.6924	pathogenic	-0.453	Destabilizing	0.078	N	0.327	neutral	None	None	None	None	N
K/H	0.4444	ambiguous	0.517	ambiguous	-0.608	Destabilizing	0.999	D	0.605	neutral	None	None	None	None	N
K/I	0.7164	likely_pathogenic	0.7724	pathogenic	0.467	Stabilizing	0.945	D	0.657	neutral	None	None	None	None	N
K/L	0.671	likely_pathogenic	0.7261	pathogenic	0.467	Stabilizing	0.85	D	0.505	neutral	None	None	None	None	N
K/M	0.5665	likely_pathogenic	0.6317	pathogenic	0.033	Stabilizing	0.995	D	0.599	neutral	N	0.488080688	None	None	N
K/N	0.6986	likely_pathogenic	0.7558	pathogenic	-0.057	Destabilizing	0.986	D	0.503	neutral	N	0.516534575	None	None	N
K/P	0.9404	likely_pathogenic	0.955	pathogenic	0.278	Stabilizing	0.998	D	0.618	neutral	None	None	None	None	N
K/Q	0.2226	likely_benign	0.2683	benign	-0.091	Destabilizing	0.897	D	0.531	neutral	N	0.500970476	None	None	N
K/R	0.0825	likely_benign	0.0873	benign	-0.163	Destabilizing	0.027	N	0.24	neutral	N	0.435748349	None	None	N
K/S	0.6546	likely_pathogenic	0.7134	pathogenic	-0.551	Destabilizing	0.964	D	0.482	neutral	None	None	None	None	N
K/T	0.4209	ambiguous	0.4738	ambiguous	-0.304	Destabilizing	0.978	D	0.552	neutral	N	0.476456034	None	None	N
K/V	0.6569	likely_pathogenic	0.7154	pathogenic	0.278	Stabilizing	0.882	D	0.609	neutral	None	None	None	None	N
K/W	0.8801	likely_pathogenic	0.919	pathogenic	-0.162	Destabilizing	1.0	D	0.675	neutral	None	None	None	None	N
K/Y	0.8319	likely_pathogenic	0.8762	pathogenic	0.159	Stabilizing	0.965	D	0.639	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.