TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7475	22648;22649;22650	chr2:178722364;178722363;178722362	chr2:179587091;179587090;179587089
N2AB	7158	21697;21698;21699	chr2:178722364;178722363;178722362	chr2:179587091;179587090;179587089
N2A	6231	18916;18917;18918	chr2:178722364;178722363;178722362	chr2:179587091;179587090;179587089
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: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-59
• Domain position: 57
• Structural Position: 137
• Q(SASA): 0.2441
• 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
T/A	None	None	0.206	D	0.398	0.295	0.176091768786	gnomAD-4.0.0	1.59232E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86002E-06	0	0
T/S	None	None	0.007	N	0.257	0.163	0.134241683229	gnomAD-4.0.0	1.59236E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02737E-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
T/A	0.0999	likely_benign	0.0994	benign	-1.147	Destabilizing	0.206	N	0.398	neutral	D	0.530099384	None	None	N
T/C	0.4811	ambiguous	0.5166	ambiguous	-0.848	Destabilizing	0.999	D	0.567	neutral	None	None	None	None	N
T/D	0.5326	ambiguous	0.5681	pathogenic	-1.451	Destabilizing	0.837	D	0.528	neutral	None	None	None	None	N
T/E	0.3493	ambiguous	0.3862	ambiguous	-1.301	Destabilizing	0.945	D	0.518	neutral	None	None	None	None	N
T/F	0.2131	likely_benign	0.2481	benign	-0.988	Destabilizing	0.998	D	0.604	neutral	None	None	None	None	N
T/G	0.3922	ambiguous	0.4059	ambiguous	-1.518	Destabilizing	0.956	D	0.563	neutral	None	None	None	None	N
T/H	0.2645	likely_benign	0.3017	benign	-1.743	Destabilizing	0.999	D	0.627	neutral	None	None	None	None	N
T/I	0.1284	likely_benign	0.1569	benign	-0.193	Destabilizing	0.9	D	0.507	neutral	N	0.52036518	None	None	N
T/K	0.2853	likely_benign	0.3445	ambiguous	-0.598	Destabilizing	0.96	D	0.513	neutral	None	None	None	None	N
T/L	0.1101	likely_benign	0.1251	benign	-0.193	Destabilizing	0.832	D	0.484	neutral	None	None	None	None	N
T/M	0.0903	likely_benign	0.0944	benign	-0.082	Destabilizing	0.994	D	0.579	neutral	None	None	None	None	N
T/N	0.1694	likely_benign	0.1909	benign	-1.143	Destabilizing	0.795	D	0.52	neutral	N	0.48866266	None	None	N
T/P	0.7912	likely_pathogenic	0.7641	pathogenic	-0.48	Destabilizing	0.965	D	0.569	neutral	D	0.531721251	None	None	N
T/Q	0.2487	likely_benign	0.2861	benign	-1.059	Destabilizing	0.988	D	0.563	neutral	None	None	None	None	N
T/R	0.2073	likely_benign	0.2552	benign	-0.686	Destabilizing	0.996	D	0.557	neutral	None	None	None	None	N
T/S	0.1186	likely_benign	0.1288	benign	-1.342	Destabilizing	0.007	N	0.257	neutral	N	0.462199523	None	None	N
T/V	0.1063	likely_benign	0.1256	benign	-0.48	Destabilizing	0.022	N	0.223	neutral	None	None	None	None	N
T/W	0.6018	likely_pathogenic	0.6347	pathogenic	-1.095	Destabilizing	1.0	D	0.666	neutral	None	None	None	None	N
T/Y	0.2871	likely_benign	0.3114	benign	-0.729	Destabilizing	0.999	D	0.626	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.