TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19854	59785;59786;59787	chr2:178592445;178592444;178592443	chr2:179457172;179457171;179457170
N2AB	18213	54862;54863;54864	chr2:178592445;178592444;178592443	chr2:179457172;179457171;179457170
N2A	17286	52081;52082;52083	chr2:178592445;178592444;178592443	chr2:179457172;179457171;179457170
N2B	10789	32590;32591;32592	chr2:178592445;178592444;178592443	chr2:179457172;179457171;179457170
Novex-1	10914	32965;32966;32967	chr2:178592445;178592444;178592443	chr2:179457172;179457171;179457170
Novex-2	10981	33166;33167;33168	chr2:178592445;178592444;178592443	chr2:179457172;179457171;179457170
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-119
• Domain position: 65
• Structural Position: 153
• Q(SASA): 0.2962
• 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/T	rs1291718498	-1.589	0.001	N	0.205	0.109	0.603063929177	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	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	0.3422	ambiguous	0.2576	benign	-1.632	Destabilizing	0.129	N	0.332	neutral	None	None	None	None	N
I/C	0.586	likely_pathogenic	0.5001	ambiguous	-1.093	Destabilizing	0.94	D	0.481	neutral	None	None	None	None	N
I/D	0.5632	ambiguous	0.5216	ambiguous	-0.482	Destabilizing	0.001	N	0.389	neutral	None	None	None	None	N
I/E	0.5335	ambiguous	0.4808	ambiguous	-0.432	Destabilizing	0.129	N	0.379	neutral	None	None	None	None	N
I/F	0.1504	likely_benign	0.127	benign	-1.007	Destabilizing	0.655	D	0.465	neutral	N	0.516820655	None	None	N
I/G	0.6198	likely_pathogenic	0.5214	ambiguous	-1.996	Destabilizing	0.129	N	0.419	neutral	None	None	None	None	N
I/H	0.373	ambiguous	0.3187	benign	-1.107	Destabilizing	0.716	D	0.541	neutral	None	None	None	None	N
I/K	0.344	ambiguous	0.3127	benign	-0.893	Destabilizing	0.129	N	0.471	neutral	None	None	None	None	N
I/L	0.1114	likely_benign	0.0935	benign	-0.693	Destabilizing	0.017	N	0.267	neutral	N	0.463063528	None	None	N
I/M	0.1119	likely_benign	0.0876	benign	-0.64	Destabilizing	0.007	N	0.178	neutral	N	0.505872943	None	None	N
I/N	0.1912	likely_benign	0.1438	benign	-0.768	Destabilizing	0.002	N	0.373	neutral	N	0.44207218	None	None	N
I/P	0.701	likely_pathogenic	0.6166	pathogenic	-0.975	Destabilizing	0.593	D	0.553	neutral	None	None	None	None	N
I/Q	0.3901	ambiguous	0.3263	benign	-0.86	Destabilizing	0.027	N	0.361	neutral	None	None	None	None	N
I/R	0.2748	likely_benign	0.2678	benign	-0.436	Destabilizing	0.418	N	0.529	neutral	None	None	None	None	N
I/S	0.2539	likely_benign	0.1939	benign	-1.557	Destabilizing	0.101	N	0.363	neutral	N	0.477472833	None	None	N
I/T	0.1862	likely_benign	0.1386	benign	-1.377	Destabilizing	0.001	N	0.205	neutral	N	0.448286077	None	None	N
I/V	0.0855	likely_benign	0.074	benign	-0.975	Destabilizing	0.047	N	0.287	neutral	N	0.460657941	None	None	N
I/W	0.6255	likely_pathogenic	0.5893	pathogenic	-1.051	Destabilizing	0.983	D	0.552	neutral	None	None	None	None	N
I/Y	0.3574	ambiguous	0.3231	benign	-0.814	Destabilizing	0.836	D	0.527	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.