TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32689	98290;98291;98292	chr2:178540101;178540100;178540099	chr2:179404828;179404827;179404826
N2AB	31048	93367;93368;93369	chr2:178540101;178540100;178540099	chr2:179404828;179404827;179404826
N2A	30121	90586;90587;90588	chr2:178540101;178540100;178540099	chr2:179404828;179404827;179404826
N2B	23624	71095;71096;71097	chr2:178540101;178540100;178540099	chr2:179404828;179404827;179404826
Novex-1	23749	71470;71471;71472	chr2:178540101;178540100;178540099	chr2:179404828;179404827;179404826
Novex-2	23816	71671;71672;71673	chr2:178540101;178540100;178540099	chr2:179404828;179404827;179404826
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-126
• Domain position: 90
• Structural Position: 123
• Q(SASA): 0.1833
• 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
V/I	None	None	0.214	N	0.147	0.153	0.390531646278	gnomAD-4.0.0	3.21222E-06	None	None	None	None	N	None	0	0	None	0	2.77747E-05	None	1.89029E-05	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
V/A	0.7922	likely_pathogenic	0.7593	pathogenic	-1.709	Destabilizing	0.953	D	0.621	neutral	N	0.508203093	None	None	N
V/C	0.917	likely_pathogenic	0.8954	pathogenic	-1.162	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
V/D	0.9703	likely_pathogenic	0.966	pathogenic	-2.096	Highly Destabilizing	0.998	D	0.891	deleterious	None	None	None	None	N
V/E	0.948	likely_pathogenic	0.9473	pathogenic	-1.951	Destabilizing	0.998	D	0.821	deleterious	N	0.511339399	None	None	N
V/F	0.5934	likely_pathogenic	0.5504	ambiguous	-1.009	Destabilizing	0.995	D	0.751	deleterious	None	None	None	None	N
V/G	0.8234	likely_pathogenic	0.8002	pathogenic	-2.179	Highly Destabilizing	0.998	D	0.897	deleterious	N	0.509904245	None	None	N
V/H	0.9864	likely_pathogenic	0.9825	pathogenic	-1.958	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
V/I	0.0935	likely_benign	0.089	benign	-0.446	Destabilizing	0.214	N	0.147	neutral	N	0.485942309	None	None	N
V/K	0.9757	likely_pathogenic	0.9748	pathogenic	-1.574	Destabilizing	0.998	D	0.827	deleterious	None	None	None	None	N
V/L	0.473	ambiguous	0.4417	ambiguous	-0.446	Destabilizing	0.807	D	0.495	neutral	N	0.459641142	None	None	N
V/M	0.5205	ambiguous	0.4835	ambiguous	-0.376	Destabilizing	0.995	D	0.655	prob.neutral	None	None	None	None	N
V/N	0.9311	likely_pathogenic	0.9102	pathogenic	-1.661	Destabilizing	0.998	D	0.889	deleterious	None	None	None	None	N
V/P	0.9315	likely_pathogenic	0.9324	pathogenic	-0.836	Destabilizing	0.998	D	0.851	deleterious	None	None	None	None	N
V/Q	0.9648	likely_pathogenic	0.9609	pathogenic	-1.608	Destabilizing	0.998	D	0.853	deleterious	None	None	None	None	N
V/R	0.9695	likely_pathogenic	0.968	pathogenic	-1.298	Destabilizing	0.998	D	0.893	deleterious	None	None	None	None	N
V/S	0.886	likely_pathogenic	0.8465	pathogenic	-2.221	Highly Destabilizing	0.998	D	0.847	deleterious	None	None	None	None	N
V/T	0.7796	likely_pathogenic	0.7258	pathogenic	-1.947	Destabilizing	0.982	D	0.633	neutral	None	None	None	None	N
V/W	0.9842	likely_pathogenic	0.982	pathogenic	-1.488	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
V/Y	0.9329	likely_pathogenic	0.922	pathogenic	-1.092	Destabilizing	0.998	D	0.753	deleterious	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.