TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6997	21214;21215;21216	chr2:178724386;178724385;178724384	chr2:179589113;179589112;179589111
N2AB	6680	20263;20264;20265	chr2:178724386;178724385;178724384	chr2:179589113;179589112;179589111
N2A	5753	17482;17483;17484	chr2:178724386;178724385;178724384	chr2:179589113;179589112;179589111
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: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-54
• Domain position: 50
• Structural Position: 125
• Q(SASA): 0.245
• 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
S/I	rs1003049715	0.477	0.473	N	0.54	0.226	0.524533156562	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
S/I	rs1003049715	0.477	0.473	N	0.54	0.226	0.524533156562	gnomAD-4.0.0	7.95938E-06	None	None	None	None	N	None	0	0	None	0	1.38696E-04	None	0	0	0	0	0
S/N	None	None	0.642	N	0.361	0.185	0.170165803431	gnomAD-4.0.0	4.77563E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85946E-06	1.43299E-05	3.02627E-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
S/A	0.1214	likely_benign	0.1225	benign	-0.536	Destabilizing	0.176	N	0.276	neutral	None	None	None	None	N
S/C	0.2259	likely_benign	0.2566	benign	-0.325	Destabilizing	0.993	D	0.465	neutral	N	0.486848553	None	None	N
S/D	0.6839	likely_pathogenic	0.6854	pathogenic	0.414	Stabilizing	0.704	D	0.332	neutral	None	None	None	None	N
S/E	0.7873	likely_pathogenic	0.8008	pathogenic	0.354	Stabilizing	0.329	N	0.33	neutral	None	None	None	None	N
S/F	0.269	likely_benign	0.2753	benign	-0.967	Destabilizing	0.893	D	0.541	neutral	None	None	None	None	N
S/G	0.1762	likely_benign	0.1714	benign	-0.699	Destabilizing	0.425	N	0.331	neutral	N	0.482862797	None	None	N
S/H	0.4924	ambiguous	0.5133	ambiguous	-1.129	Destabilizing	0.017	N	0.295	neutral	None	None	None	None	N
S/I	0.2277	likely_benign	0.2283	benign	-0.23	Destabilizing	0.473	N	0.54	neutral	N	0.468490778	None	None	N
S/K	0.8964	likely_pathogenic	0.9066	pathogenic	-0.436	Destabilizing	0.329	N	0.323	neutral	None	None	None	None	N
S/L	0.1361	likely_benign	0.1365	benign	-0.23	Destabilizing	0.007	N	0.344	neutral	None	None	None	None	N
S/M	0.2945	likely_benign	0.3087	benign	-0.036	Destabilizing	0.893	D	0.5	neutral	None	None	None	None	N
S/N	0.2942	likely_benign	0.2891	benign	-0.213	Destabilizing	0.642	D	0.361	neutral	N	0.477763622	None	None	N
S/P	0.8695	likely_pathogenic	0.865	pathogenic	-0.301	Destabilizing	0.828	D	0.521	neutral	None	None	None	None	N
S/Q	0.702	likely_pathogenic	0.7299	pathogenic	-0.401	Destabilizing	0.085	N	0.241	neutral	None	None	None	None	N
S/R	0.8042	likely_pathogenic	0.8278	pathogenic	-0.287	Destabilizing	0.006	N	0.314	neutral	N	0.45794571	None	None	N
S/T	0.0953	likely_benign	0.0973	benign	-0.341	Destabilizing	0.01	N	0.12	neutral	N	0.422350269	None	None	N
S/V	0.249	likely_benign	0.2475	benign	-0.301	Destabilizing	0.543	D	0.495	neutral	None	None	None	None	N
S/W	0.4794	ambiguous	0.5081	ambiguous	-0.937	Destabilizing	0.995	D	0.576	neutral	None	None	None	None	N
S/Y	0.2664	likely_benign	0.2791	benign	-0.67	Destabilizing	0.893	D	0.552	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.