TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25705	77338;77339;77340	chr2:178569019;178569018;178569017	chr2:179433746;179433745;179433744
N2AB	24064	72415;72416;72417	chr2:178569019;178569018;178569017	chr2:179433746;179433745;179433744
N2A	23137	69634;69635;69636	chr2:178569019;178569018;178569017	chr2:179433746;179433745;179433744
N2B	16640	50143;50144;50145	chr2:178569019;178569018;178569017	chr2:179433746;179433745;179433744
Novex-1	16765	50518;50519;50520	chr2:178569019;178569018;178569017	chr2:179433746;179433745;179433744
Novex-2	16832	50719;50720;50721	chr2:178569019;178569018;178569017	chr2:179433746;179433745;179433744
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Fn3-75
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.1147
• 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	rs561858074	-2.746	0.634	N	0.699	0.438	0.672566338644	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
I/T	rs561858074	-2.746	0.634	N	0.699	0.438	0.672566338644	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	1.4E-03	None	None	0	0	None	None	None	0	None
I/T	rs561858074	-2.746	0.634	N	0.699	0.438	0.672566338644	gnomAD-4.0.0	6.57583E-06	None	None	None	None	N	None	0	6.5505E-05	None	0	0	None	0	0	0	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	0.9426	likely_pathogenic	0.9181	pathogenic	-2.295	Highly Destabilizing	0.759	D	0.648	neutral	None	None	None	None	N
I/C	0.9538	likely_pathogenic	0.9388	pathogenic	-1.669	Destabilizing	0.998	D	0.678	prob.neutral	None	None	None	None	N
I/D	0.9963	likely_pathogenic	0.9944	pathogenic	-2.203	Highly Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
I/E	0.9921	likely_pathogenic	0.9886	pathogenic	-2.03	Highly Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	N
I/F	0.6595	likely_pathogenic	0.5539	ambiguous	-1.407	Destabilizing	0.932	D	0.755	deleterious	None	None	None	None	N
I/G	0.9856	likely_pathogenic	0.9796	pathogenic	-2.802	Highly Destabilizing	0.982	D	0.753	deleterious	None	None	None	None	N
I/H	0.9927	likely_pathogenic	0.9884	pathogenic	-2.233	Highly Destabilizing	0.996	D	0.757	deleterious	None	None	None	None	N
I/K	0.9873	likely_pathogenic	0.9809	pathogenic	-1.689	Destabilizing	0.974	D	0.752	deleterious	N	0.495032901	None	None	N
I/L	0.1924	likely_benign	0.1526	benign	-0.865	Destabilizing	None	N	0.259	neutral	N	0.372861945	None	None	N
I/M	0.2502	likely_benign	0.2009	benign	-0.822	Destabilizing	0.282	N	0.669	neutral	D	0.522175255	None	None	N
I/N	0.9497	likely_pathogenic	0.9267	pathogenic	-1.859	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
I/P	0.9723	likely_pathogenic	0.9646	pathogenic	-1.318	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
I/Q	0.9887	likely_pathogenic	0.9831	pathogenic	-1.792	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
I/R	0.9853	likely_pathogenic	0.9774	pathogenic	-1.371	Destabilizing	0.998	D	0.771	deleterious	N	0.483676596	None	None	N
I/S	0.9695	likely_pathogenic	0.9542	pathogenic	-2.597	Highly Destabilizing	0.982	D	0.725	prob.delet.	None	None	None	None	N
I/T	0.9467	likely_pathogenic	0.9225	pathogenic	-2.279	Highly Destabilizing	0.634	D	0.699	prob.neutral	N	0.483169617	None	None	N
I/V	0.1315	likely_benign	0.1247	benign	-1.318	Destabilizing	None	N	0.194	neutral	N	0.388028973	None	None	N
I/W	0.989	likely_pathogenic	0.9819	pathogenic	-1.722	Destabilizing	0.999	D	0.762	deleterious	None	None	None	None	N
I/Y	0.9549	likely_pathogenic	0.9343	pathogenic	-1.427	Destabilizing	0.717	D	0.729	prob.delet.	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.