TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3317	10174;10175;10176	chr2:178764566;178764565;178764564	chr2:179629293;179629292;179629291
N2AB	3317	10174;10175;10176	chr2:178764566;178764565;178764564	chr2:179629293;179629292;179629291
N2A	3317	10174;10175;10176	chr2:178764566;178764565;178764564	chr2:179629293;179629292;179629291
N2B	3271	10036;10037;10038	chr2:178764566;178764565;178764564	chr2:179629293;179629292;179629291
Novex-1	3271	10036;10037;10038	chr2:178764566;178764565;178764564	chr2:179629293;179629292;179629291
Novex-2	3271	10036;10037;10038	chr2:178764566;178764565;178764564	chr2:179629293;179629292;179629291
Novex-3	3317	10174;10175;10176	chr2:178764566;178764565;178764564	chr2:179629293;179629292;179629291

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-23
• Domain position: 79
• Structural Position: 163
• Q(SASA): 0.8834
• Predicted PPI site: I

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
Y/C	rs768476150	0.364	0.999	D	0.605	0.554	0.614776886339	gnomAD-2.1.1	1.99E-05	None	None	None	None	I	None	0	2.89E-05	None	0	0	None	0	None	0	3.54E-05	0
Y/C	rs768476150	0.364	0.999	D	0.605	0.554	0.614776886339	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	4.77555E-04
Y/C	rs768476150	0.364	0.999	D	0.605	0.554	0.614776886339	gnomAD-4.0.0	1.28053E-05	None	None	None	None	I	None	0	1.69434E-05	None	0	2.42377E-05	None	0	0	1.67417E-05	0	2.84236E-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
Y/A	0.7238	likely_pathogenic	0.5524	ambiguous	-0.38	Destabilizing	0.91	D	0.563	neutral	None	None	None	None	I
Y/C	0.3456	ambiguous	0.2188	benign	0.261	Stabilizing	0.999	D	0.605	neutral	D	0.551837373	None	None	I
Y/D	0.4888	ambiguous	0.4236	ambiguous	0.813	Stabilizing	0.982	D	0.595	neutral	D	0.56575136	None	None	I
Y/E	0.8578	likely_pathogenic	0.7706	pathogenic	0.781	Stabilizing	0.986	D	0.527	neutral	None	None	None	None	I
Y/F	0.1559	likely_benign	0.1202	benign	-0.237	Destabilizing	0.99	D	0.568	neutral	N	0.493014267	None	None	I
Y/G	0.6877	likely_pathogenic	0.5415	ambiguous	-0.539	Destabilizing	0.91	D	0.552	neutral	None	None	None	None	I
Y/H	0.3819	ambiguous	0.2898	benign	0.333	Stabilizing	0.997	D	0.596	neutral	N	0.507580693	None	None	I
Y/I	0.806	likely_pathogenic	0.6811	pathogenic	None	Stabilizing	0.993	D	0.597	neutral	None	None	None	None	I
Y/K	0.865	likely_pathogenic	0.8151	pathogenic	0.347	Stabilizing	0.986	D	0.537	neutral	None	None	None	None	I
Y/L	0.721	likely_pathogenic	0.6556	pathogenic	None	Stabilizing	0.953	D	0.628	neutral	None	None	None	None	I
Y/M	0.8599	likely_pathogenic	0.761	pathogenic	0.015	Stabilizing	0.999	D	0.593	neutral	None	None	None	None	I
Y/N	0.3867	ambiguous	0.2952	benign	0.152	Stabilizing	0.982	D	0.581	neutral	N	0.507624979	None	None	I
Y/P	0.9819	likely_pathogenic	0.9749	pathogenic	-0.107	Destabilizing	0.993	D	0.607	neutral	None	None	None	None	I
Y/Q	0.8085	likely_pathogenic	0.6967	pathogenic	0.204	Stabilizing	0.993	D	0.591	neutral	None	None	None	None	I
Y/R	0.6957	likely_pathogenic	0.6186	pathogenic	0.512	Stabilizing	0.986	D	0.589	neutral	None	None	None	None	I
Y/S	0.4031	ambiguous	0.2294	benign	-0.18	Destabilizing	0.322	N	0.561	neutral	N	0.495615845	None	None	I
Y/T	0.7414	likely_pathogenic	0.573	pathogenic	-0.122	Destabilizing	0.973	D	0.515	neutral	None	None	None	None	I
Y/V	0.679	likely_pathogenic	0.5168	ambiguous	-0.107	Destabilizing	0.986	D	0.567	neutral	None	None	None	None	I
Y/W	0.6679	likely_pathogenic	0.616	pathogenic	-0.464	Destabilizing	0.999	D	0.587	neutral	None	None	None	None	I

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.