TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14919	44980;44981;44982	chr2:178624525;178624524;178624523	chr2:179489252;179489251;179489250
N2AB	13278	40057;40058;40059	chr2:178624525;178624524;178624523	chr2:179489252;179489251;179489250
N2A	12351	37276;37277;37278	chr2:178624525;178624524;178624523	chr2:179489252;179489251;179489250
N2B	5854	17785;17786;17787	chr2:178624525;178624524;178624523	chr2:179489252;179489251;179489250
Novex-1	5979	18160;18161;18162	chr2:178624525;178624524;178624523	chr2:179489252;179489251;179489250
Novex-2	6046	18361;18362;18363	chr2:178624525;178624524;178624523	chr2:179489252;179489251;179489250
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-100
• Domain position: 67
• Structural Position: 151
• Q(SASA): 0.2638
• 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/M	None	None	0.975	N	0.457	0.267	0.530803083455	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-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	0.2023	likely_benign	0.208	benign	-1.797	Destabilizing	0.001	N	0.151	neutral	None	None	None	None	N
I/C	0.5846	likely_pathogenic	0.6558	pathogenic	-0.968	Destabilizing	0.944	D	0.489	neutral	None	None	None	None	N
I/D	0.4624	ambiguous	0.4882	ambiguous	-1.391	Destabilizing	0.495	N	0.44	neutral	None	None	None	None	N
I/E	0.3045	likely_benign	0.3324	benign	-1.391	Destabilizing	0.495	N	0.4	neutral	None	None	None	None	N
I/F	0.2451	likely_benign	0.2311	benign	-1.293	Destabilizing	0.784	D	0.473	neutral	N	0.500534459	None	None	N
I/G	0.4453	ambiguous	0.4388	ambiguous	-2.122	Highly Destabilizing	0.001	N	0.308	neutral	None	None	None	None	N
I/H	0.4805	ambiguous	0.4736	ambiguous	-1.32	Destabilizing	0.981	D	0.511	neutral	None	None	None	None	N
I/K	0.2637	likely_benign	0.2845	benign	-1.298	Destabilizing	0.495	N	0.418	neutral	None	None	None	None	N
I/L	0.1859	likely_benign	0.1649	benign	-0.97	Destabilizing	0.244	N	0.283	neutral	N	0.482079375	None	None	N
I/M	0.118	likely_benign	0.1127	benign	-0.635	Destabilizing	0.975	D	0.457	neutral	N	0.452901181	None	None	N
I/N	0.1614	likely_benign	0.1679	benign	-1.09	Destabilizing	0.642	D	0.483	neutral	N	0.468182812	None	None	N
I/P	0.7993	likely_pathogenic	0.7999	pathogenic	-1.215	Destabilizing	0.828	D	0.531	neutral	None	None	None	None	N
I/Q	0.2938	likely_benign	0.3092	benign	-1.292	Destabilizing	0.828	D	0.577	neutral	None	None	None	None	N
I/R	0.2094	likely_benign	0.2223	benign	-0.625	Destabilizing	0.828	D	0.567	neutral	None	None	None	None	N
I/S	0.1322	likely_benign	0.1336	benign	-1.677	Destabilizing	0.01	N	0.237	neutral	N	0.356391719	None	None	N
I/T	0.1415	likely_benign	0.1572	benign	-1.569	Destabilizing	0.27	N	0.335	neutral	N	0.434692228	None	None	N
I/V	0.0986	likely_benign	0.092	benign	-1.215	Destabilizing	0.139	N	0.287	neutral	N	0.451245403	None	None	N
I/W	0.7864	likely_pathogenic	0.8161	pathogenic	-1.384	Destabilizing	0.995	D	0.523	neutral	None	None	None	None	N
I/Y	0.4919	ambiguous	0.5254	ambiguous	-1.183	Destabilizing	0.981	D	0.573	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.