TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6809	20650;20651;20652	chr2:178725897;178725896;178725895	chr2:179590624;179590623;179590622
N2AB	6492	19699;19700;19701	chr2:178725897;178725896;178725895	chr2:179590624;179590623;179590622
N2A	5565	16918;16919;16920	chr2:178725897;178725896;178725895	chr2:179590624;179590623;179590622
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: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-52
• Domain position: 49
• Structural Position: 123
• Q(SASA): 0.2932
• 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
I/F	None	None	None	N	0.111	0.16	0.351614576976	gnomAD-4.0.0	1.59281E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8608E-06	0	0
I/T	rs879197315	-1.512	0.09	N	0.479	0.325	None	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.14943E-04	0	None	0	0	None	0	None	0	0	0
I/T	rs879197315	-1.512	0.09	N	0.479	0.325	None	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	1.20814E-04	0	0	0	0	None	0	0	0	0	0
I/T	rs879197315	-1.512	0.09	N	0.479	0.325	None	gnomAD-4.0.0	6.19994E-06	None	None	None	None	N	None	9.35529E-05	0	None	0	0	None	0	0	2.54355E-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
I/A	0.3755	ambiguous	0.4277	ambiguous	-1.953	Destabilizing	0.153	N	0.429	neutral	None	None	None	None	N
I/C	0.7993	likely_pathogenic	0.8584	pathogenic	-1.347	Destabilizing	0.959	D	0.545	neutral	None	None	None	None	N
I/D	0.9166	likely_pathogenic	0.9344	pathogenic	-1.145	Destabilizing	0.862	D	0.623	neutral	None	None	None	None	N
I/E	0.8173	likely_pathogenic	0.853	pathogenic	-1.056	Destabilizing	0.821	D	0.631	neutral	None	None	None	None	N
I/F	0.1658	likely_benign	0.1791	benign	-1.234	Destabilizing	None	N	0.111	neutral	N	0.521439828	None	None	N
I/G	0.7835	likely_pathogenic	0.8388	pathogenic	-2.374	Highly Destabilizing	0.862	D	0.619	neutral	None	None	None	None	N
I/H	0.7716	likely_pathogenic	0.7941	pathogenic	-1.566	Destabilizing	0.967	D	0.612	neutral	None	None	None	None	N
I/K	0.709	likely_pathogenic	0.7588	pathogenic	-1.263	Destabilizing	0.155	N	0.631	neutral	None	None	None	None	N
I/L	0.1299	likely_benign	0.1582	benign	-0.823	Destabilizing	0.002	N	0.275	neutral	N	0.496445383	None	None	N
I/M	0.0962	likely_benign	0.1051	benign	-0.744	Destabilizing	0.217	N	0.533	neutral	D	0.531520749	None	None	N
I/N	0.5677	likely_pathogenic	0.6028	pathogenic	-1.209	Destabilizing	0.935	D	0.63	neutral	D	0.528794736	None	None	N
I/P	0.8746	likely_pathogenic	0.9069	pathogenic	-1.17	Destabilizing	0.95	D	0.623	neutral	None	None	None	None	N
I/Q	0.6878	likely_pathogenic	0.7212	pathogenic	-1.258	Destabilizing	0.887	D	0.619	neutral	None	None	None	None	N
I/R	0.6039	likely_pathogenic	0.667	pathogenic	-0.822	Destabilizing	0.712	D	0.631	neutral	None	None	None	None	N
I/S	0.4603	ambiguous	0.5133	ambiguous	-1.986	Destabilizing	0.398	N	0.581	neutral	N	0.506309161	None	None	N
I/T	0.2124	likely_benign	0.2359	benign	-1.758	Destabilizing	0.09	N	0.479	neutral	N	0.497243807	None	None	N
I/V	0.0759	likely_benign	0.0826	benign	-1.17	Destabilizing	None	N	0.121	neutral	N	0.479856991	None	None	N
I/W	0.8094	likely_pathogenic	0.8365	pathogenic	-1.352	Destabilizing	0.991	D	0.616	neutral	None	None	None	None	N
I/Y	0.5685	likely_pathogenic	0.6094	pathogenic	-1.105	Destabilizing	0.02	N	0.535	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.