TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35481	106666;106667;106668	chr2:178530050;178530049;178530048	chr2:179394777;179394776;179394775
N2AB	33840	101743;101744;101745	chr2:178530050;178530049;178530048	chr2:179394777;179394776;179394775
N2A	32913	98962;98963;98964	chr2:178530050;178530049;178530048	chr2:179394777;179394776;179394775
N2B	26416	79471;79472;79473	chr2:178530050;178530049;178530048	chr2:179394777;179394776;179394775
Novex-1	26541	79846;79847;79848	chr2:178530050;178530049;178530048	chr2:179394777;179394776;179394775
Novex-2	26608	80047;80048;80049	chr2:178530050;178530049;178530048	chr2:179394777;179394776;179394775
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: Ig-166
• Domain position: 62
• Structural Position: 143
• Q(SASA): 0.5389
• 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/R	rs200716018	0.253	0.157	N	0.337	0.135	None	gnomAD-2.1.1	4.67E-05	None	None	None	None	N	None	8.28E-05	5.74E-05	None	0	0	None	0	None	0	6.26E-05	1.40964E-04
K/R	rs200716018	0.253	0.157	N	0.337	0.135	None	gnomAD-3.1.2	1.05128E-04	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	2.20504E-04	0	0
K/R	rs200716018	0.253	0.157	N	0.337	0.135	None	gnomAD-4.0.0	1.60703E-04	None	None	None	None	N	None	1.33618E-05	0	None	0	0	None	0	0	2.00969E-04	0	3.36636E-04

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	0.2732	likely_benign	0.2801	benign	-0.081	Destabilizing	0.049	N	0.371	neutral	None	None	None	None	N
K/C	0.7447	likely_pathogenic	0.767	pathogenic	-0.048	Destabilizing	0.953	D	0.348	neutral	None	None	None	None	N
K/D	0.4062	ambiguous	0.4247	ambiguous	0.055	Stabilizing	None	N	0.128	neutral	None	None	None	None	N
K/E	0.1162	likely_benign	0.1154	benign	0.084	Stabilizing	None	N	0.093	neutral	N	0.413111058	None	None	N
K/F	0.7423	likely_pathogenic	0.7628	pathogenic	-0.162	Destabilizing	0.842	D	0.381	neutral	None	None	None	None	N
K/G	0.3212	likely_benign	0.3331	benign	-0.343	Destabilizing	0.092	N	0.377	neutral	None	None	None	None	N
K/H	0.3096	likely_benign	0.3517	ambiguous	-0.751	Destabilizing	0.637	D	0.355	neutral	None	None	None	None	N
K/I	0.3941	ambiguous	0.3941	ambiguous	0.547	Stabilizing	0.637	D	0.407	neutral	None	None	None	None	N
K/L	0.3635	ambiguous	0.3722	ambiguous	0.547	Stabilizing	0.198	N	0.413	neutral	None	None	None	None	N
K/M	0.2452	likely_benign	0.2568	benign	0.494	Stabilizing	0.801	D	0.355	neutral	N	0.484512583	None	None	N
K/N	0.2713	likely_benign	0.2914	benign	0.248	Stabilizing	0.157	N	0.308	neutral	N	0.361775373	None	None	N
K/P	0.7239	likely_pathogenic	0.6413	pathogenic	0.368	Stabilizing	0.334	N	0.411	neutral	None	None	None	None	N
K/Q	0.1146	likely_benign	0.1252	benign	0.053	Stabilizing	0.085	N	0.33	neutral	N	0.431390174	None	None	N
K/R	0.0927	likely_benign	0.0982	benign	-0.089	Destabilizing	0.157	N	0.337	neutral	N	0.380942711	None	None	N
K/S	0.2952	likely_benign	0.3068	benign	-0.293	Destabilizing	0.049	N	0.367	neutral	None	None	None	None	N
K/T	0.1646	likely_benign	0.1695	benign	-0.096	Destabilizing	0.157	N	0.363	neutral	N	0.447994422	None	None	N
K/V	0.3645	ambiguous	0.3726	ambiguous	0.368	Stabilizing	0.198	N	0.433	neutral	None	None	None	None	N
K/W	0.8089	likely_pathogenic	0.8257	pathogenic	-0.117	Destabilizing	0.953	D	0.414	neutral	None	None	None	None	N
K/Y	0.6141	likely_pathogenic	0.6321	pathogenic	0.223	Stabilizing	0.842	D	0.384	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.