TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6376	19351;19352;19353	chr2:178728912;178728911;178728910	chr2:179593639;179593638;179593637
N2AB	6059	18400;18401;18402	chr2:178728912;178728911;178728910	chr2:179593639;179593638;179593637
N2A	5132	15619;15620;15621	chr2:178728912;178728911;178728910	chr2:179593639;179593638;179593637
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: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-47
• Domain position: 85
• Structural Position: 171
• Q(SASA): 0.6344
• 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	rs747117289	-0.588	0.56	N	0.54	0.206	0.471132149292	gnomAD-2.1.1	4.1E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.41E-05	None	0	0	0
Y/C	rs747117289	-0.588	0.56	N	0.54	0.206	0.471132149292	gnomAD-4.0.0	1.37537E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.35056E-05	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
Y/A	0.3905	ambiguous	0.3427	ambiguous	-1.648	Destabilizing	0.007	N	0.388	neutral	None	None	None	None	I
Y/C	0.1838	likely_benign	0.1534	benign	-0.322	Destabilizing	0.56	D	0.54	neutral	N	0.486516391	None	None	I
Y/D	0.2512	likely_benign	0.2069	benign	-0.008	Destabilizing	0.055	N	0.537	neutral	N	0.433777984	None	None	I
Y/E	0.537	ambiguous	0.4867	ambiguous	0.024	Stabilizing	0.072	N	0.515	neutral	None	None	None	None	I
Y/F	0.0832	likely_benign	0.0833	benign	-0.791	Destabilizing	None	N	0.198	neutral	N	0.377695415	None	None	I
Y/G	0.3977	ambiguous	0.3609	ambiguous	-1.914	Destabilizing	0.031	N	0.431	neutral	None	None	None	None	I
Y/H	0.1472	likely_benign	0.1371	benign	-0.492	Destabilizing	0.56	D	0.516	neutral	N	0.41013312	None	None	I
Y/I	0.4263	ambiguous	0.3805	ambiguous	-0.888	Destabilizing	0.016	N	0.403	neutral	None	None	None	None	I
Y/K	0.5884	likely_pathogenic	0.5467	ambiguous	-0.558	Destabilizing	0.072	N	0.527	neutral	None	None	None	None	I
Y/L	0.4476	ambiguous	0.4189	ambiguous	-0.888	Destabilizing	0.007	N	0.319	neutral	None	None	None	None	I
Y/M	0.5682	likely_pathogenic	0.5322	ambiguous	-0.535	Destabilizing	0.356	N	0.538	neutral	None	None	None	None	I
Y/N	0.1476	likely_benign	0.1337	benign	-0.77	Destabilizing	0.055	N	0.555	neutral	N	0.428372164	None	None	I
Y/P	0.8078	likely_pathogenic	0.7232	pathogenic	-1.129	Destabilizing	0.356	N	0.587	neutral	None	None	None	None	I
Y/Q	0.4169	ambiguous	0.3809	ambiguous	-0.732	Destabilizing	0.356	N	0.57	neutral	None	None	None	None	I
Y/R	0.4329	ambiguous	0.3933	ambiguous	-0.148	Destabilizing	0.356	N	0.591	neutral	None	None	None	None	I
Y/S	0.1231	likely_benign	0.1161	benign	-1.252	Destabilizing	0.001	N	0.359	neutral	N	0.311987711	None	None	I
Y/T	0.2746	likely_benign	0.2455	benign	-1.128	Destabilizing	0.016	N	0.424	neutral	None	None	None	None	I
Y/V	0.3098	likely_benign	0.2712	benign	-1.129	Destabilizing	None	N	0.267	neutral	None	None	None	None	I
Y/W	0.4457	ambiguous	0.4109	ambiguous	-0.621	Destabilizing	0.356	N	0.543	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.