TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8892	26899;26900;26901	chr2:178713984;178713983;178713982	chr2:179578711;179578710;179578709
N2AB	8575	25948;25949;25950	chr2:178713984;178713983;178713982	chr2:179578711;179578710;179578709
N2A	7648	23167;23168;23169	chr2:178713984;178713983;178713982	chr2:179578711;179578710;179578709
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: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-74
• Domain position: 63
• Structural Position: 144
• Q(SASA): 0.0782
• 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
V/I	rs747832107	-0.491	0.042	D	0.447	0.119	0.342631996419	gnomAD-2.1.1	6.43E-05	None	None	None	None	N	None	0	5.10204E-04	None	0	0	None	0	None	0	0	0
V/I	rs747832107	-0.491	0.042	D	0.447	0.119	0.342631996419	gnomAD-3.1.2	8.54E-05	None	None	None	None	N	None	0	8.51566E-04	0	0	0	None	0	0	0	0	0
V/I	rs747832107	-0.491	0.042	D	0.447	0.119	0.342631996419	gnomAD-4.0.0	3.844E-05	None	None	None	None	N	None	0	4.74737E-04	None	0	0	None	0	0	0	1.34052E-05	2.84544E-05

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
V/A	0.0999	likely_benign	0.1033	benign	-1.864	Destabilizing	None	N	0.17	neutral	N	0.450174376	None	None	N
V/C	0.7471	likely_pathogenic	0.7869	pathogenic	-2.485	Highly Destabilizing	0.667	D	0.625	neutral	None	None	None	None	N
V/D	0.8807	likely_pathogenic	0.9079	pathogenic	-3.58	Highly Destabilizing	0.22	N	0.637	neutral	None	None	None	None	N
V/E	0.8663	likely_pathogenic	0.8988	pathogenic	-3.478	Highly Destabilizing	0.175	N	0.557	neutral	D	0.548018762	None	None	N
V/F	0.6223	likely_pathogenic	0.7073	pathogenic	-1.341	Destabilizing	0.22	N	0.638	neutral	None	None	None	None	N
V/G	0.3241	likely_benign	0.362	ambiguous	-2.225	Highly Destabilizing	0.042	N	0.511	neutral	N	0.521520716	None	None	N
V/H	0.948	likely_pathogenic	0.967	pathogenic	-1.675	Destabilizing	0.859	D	0.659	neutral	None	None	None	None	N
V/I	0.1169	likely_benign	0.1359	benign	-0.901	Destabilizing	0.042	N	0.447	neutral	D	0.52538421	None	None	N
V/K	0.918	likely_pathogenic	0.945	pathogenic	-1.878	Destabilizing	0.22	N	0.553	neutral	None	None	None	None	N
V/L	0.3894	ambiguous	0.488	ambiguous	-0.901	Destabilizing	None	N	0.222	neutral	D	0.523232126	None	None	N
V/M	0.3152	likely_benign	0.3995	ambiguous	-1.242	Destabilizing	0.004	N	0.377	neutral	None	None	None	None	N
V/N	0.7294	likely_pathogenic	0.7864	pathogenic	-2.286	Highly Destabilizing	0.22	N	0.655	neutral	None	None	None	None	N
V/P	0.7451	likely_pathogenic	0.8258	pathogenic	-1.197	Destabilizing	0.364	N	0.633	neutral	None	None	None	None	N
V/Q	0.8712	likely_pathogenic	0.9041	pathogenic	-2.377	Highly Destabilizing	0.364	N	0.657	neutral	None	None	None	None	N
V/R	0.8744	likely_pathogenic	0.9018	pathogenic	-1.414	Destabilizing	0.22	N	0.674	neutral	None	None	None	None	N
V/S	0.2653	likely_benign	0.2917	benign	-2.673	Highly Destabilizing	0.005	N	0.467	neutral	None	None	None	None	N
V/T	0.1477	likely_benign	0.1597	benign	-2.459	Highly Destabilizing	0.002	N	0.184	neutral	None	None	None	None	N
V/W	0.9843	likely_pathogenic	0.9934	pathogenic	-1.71	Destabilizing	0.958	D	0.632	neutral	None	None	None	None	N
V/Y	0.9341	likely_pathogenic	0.961	pathogenic	-1.392	Destabilizing	0.667	D	0.661	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.