TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32161	96706;96707;96708	chr2:178543492;178543491;178543490	chr2:179408219;179408218;179408217
N2AB	30520	91783;91784;91785	chr2:178543492;178543491;178543490	chr2:179408219;179408218;179408217
N2A	29593	89002;89003;89004	chr2:178543492;178543491;178543490	chr2:179408219;179408218;179408217
N2B	23096	69511;69512;69513	chr2:178543492;178543491;178543490	chr2:179408219;179408218;179408217
Novex-1	23221	69886;69887;69888	chr2:178543492;178543491;178543490	chr2:179408219;179408218;179408217
Novex-2	23288	70087;70088;70089	chr2:178543492;178543491;178543490	chr2:179408219;179408218;179408217
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: Fn3-122
• Domain position: 57
• Structural Position: 88
• Q(SASA): 0.4765
• 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	None	None	1.0	N	0.653	0.466	0.369682402691	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	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	0.8084	likely_pathogenic	0.7211	pathogenic	-0.096	Destabilizing	1.0	D	0.646	neutral	None	None	None	None	N
K/C	0.9278	likely_pathogenic	0.8866	pathogenic	-0.429	Destabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
K/D	0.8924	likely_pathogenic	0.847	pathogenic	0.105	Stabilizing	1.0	D	0.671	neutral	None	None	None	None	N
K/E	0.7049	likely_pathogenic	0.562	ambiguous	0.156	Stabilizing	0.998	D	0.566	neutral	N	0.442748892	None	None	N
K/F	0.9838	likely_pathogenic	0.9696	pathogenic	-0.176	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
K/G	0.7951	likely_pathogenic	0.7149	pathogenic	-0.328	Destabilizing	1.0	D	0.597	neutral	None	None	None	None	N
K/H	0.6248	likely_pathogenic	0.5186	ambiguous	-0.443	Destabilizing	1.0	D	0.643	neutral	None	None	None	None	N
K/I	0.9342	likely_pathogenic	0.8884	pathogenic	0.448	Stabilizing	0.996	D	0.674	neutral	None	None	None	None	N
K/L	0.8678	likely_pathogenic	0.7969	pathogenic	0.448	Stabilizing	0.996	D	0.597	neutral	None	None	None	None	N
K/M	0.8127	likely_pathogenic	0.7055	pathogenic	-0.014	Destabilizing	1.0	D	0.636	neutral	N	0.517212152	None	None	N
K/N	0.85	likely_pathogenic	0.7705	pathogenic	-0.03	Destabilizing	1.0	D	0.667	neutral	N	0.493796575	None	None	N
K/P	0.9593	likely_pathogenic	0.9443	pathogenic	0.295	Stabilizing	1.0	D	0.663	neutral	None	None	None	None	N
K/Q	0.388	ambiguous	0.2858	benign	-0.079	Destabilizing	0.999	D	0.649	neutral	N	0.474170664	None	None	N
K/R	0.0995	likely_benign	0.0879	benign	-0.08	Destabilizing	0.997	D	0.523	neutral	N	0.439231371	None	None	N
K/S	0.8276	likely_pathogenic	0.7343	pathogenic	-0.511	Destabilizing	1.0	D	0.637	neutral	None	None	None	None	N
K/T	0.685	likely_pathogenic	0.5623	ambiguous	-0.292	Destabilizing	1.0	D	0.653	neutral	N	0.458755708	None	None	N
K/V	0.8755	likely_pathogenic	0.8071	pathogenic	0.295	Stabilizing	0.997	D	0.626	neutral	None	None	None	None	N
K/W	0.9707	likely_pathogenic	0.9449	pathogenic	-0.218	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	N
K/Y	0.9361	likely_pathogenic	0.9002	pathogenic	0.126	Stabilizing	0.999	D	0.636	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.