TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5585	16978;16979;16980	chr2:178732216;178732215;178732214	chr2:179596943;179596942;179596941
N2AB	5268	16027;16028;16029	chr2:178732216;178732215;178732214	chr2:179596943;179596942;179596941
N2A	4341	13246;13247;13248	chr2:178732216;178732215;178732214	chr2:179596943;179596942;179596941
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-39
• Domain position: 43
• Structural Position: 59
• Q(SASA): 0.8241
• 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/T	rs1180216660	0.184	0.001	N	0.189	0.276	0.27855597813	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	1.67019E-04	None	0	None	0	0	0
K/T	rs1180216660	0.184	0.001	N	0.189	0.276	0.27855597813	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.92976E-04	None	0	0	0	0	0
K/T	rs1180216660	0.184	0.001	N	0.189	0.276	0.27855597813	gnomAD-4.0.0	5.12397E-06	None	None	None	None	N	None	0	0	None	0	9.69885E-05	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	0.1748	likely_benign	0.2057	benign	0.047	Stabilizing	0.035	N	0.353	neutral	None	None	None	None	N
K/C	0.5218	ambiguous	0.5712	pathogenic	-0.365	Destabilizing	0.935	D	0.347	neutral	None	None	None	None	N
K/D	0.3554	ambiguous	0.4071	ambiguous	-0.238	Destabilizing	0.149	N	0.397	neutral	None	None	None	None	N
K/E	0.0971	likely_benign	0.1046	benign	-0.239	Destabilizing	0.027	N	0.336	neutral	N	0.474280599	None	None	N
K/F	0.5017	ambiguous	0.5438	ambiguous	-0.228	Destabilizing	0.555	D	0.363	neutral	None	None	None	None	N
K/G	0.2276	likely_benign	0.27	benign	-0.108	Destabilizing	None	N	0.225	neutral	None	None	None	None	N
K/H	0.2008	likely_benign	0.2318	benign	-0.229	Destabilizing	0.555	D	0.369	neutral	None	None	None	None	N
K/I	0.2154	likely_benign	0.2337	benign	0.377	Stabilizing	0.38	N	0.371	neutral	None	None	None	None	N
K/L	0.1912	likely_benign	0.2222	benign	0.377	Stabilizing	0.081	N	0.401	neutral	None	None	None	None	N
K/M	0.1515	likely_benign	0.1654	benign	-0.031	Destabilizing	0.741	D	0.367	neutral	N	0.514879215	None	None	N
K/N	0.2509	likely_benign	0.2878	benign	0.058	Stabilizing	0.117	N	0.332	neutral	N	0.476184754	None	None	N
K/P	0.3337	likely_benign	0.4074	ambiguous	0.292	Stabilizing	0.555	D	0.375	neutral	None	None	None	None	N
K/Q	0.0924	likely_benign	0.0986	benign	-0.073	Destabilizing	0.117	N	0.357	neutral	N	0.440149383	None	None	N
K/R	0.0692	likely_benign	0.0724	benign	-0.081	Destabilizing	None	N	0.246	neutral	N	0.461620733	None	None	N
K/S	0.2123	likely_benign	0.2497	benign	-0.306	Destabilizing	0.007	N	0.226	neutral	None	None	None	None	N
K/T	0.1024	likely_benign	0.1142	benign	-0.181	Destabilizing	0.001	N	0.189	neutral	N	0.432876694	None	None	N
K/V	0.1967	likely_benign	0.2192	benign	0.292	Stabilizing	0.081	N	0.411	neutral	None	None	None	None	N
K/W	0.4829	ambiguous	0.5461	ambiguous	-0.327	Destabilizing	0.935	D	0.36	neutral	None	None	None	None	N
K/Y	0.4202	ambiguous	0.4631	ambiguous	0.024	Stabilizing	0.555	D	0.365	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.