TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7076	21451;21452;21453	chr2:178724033;178724032;178724031	chr2:179588760;179588759;179588758
N2AB	6759	20500;20501;20502	chr2:178724033;178724032;178724031	chr2:179588760;179588759;179588758
N2A	5832	17719;17720;17721	chr2:178724033;178724032;178724031	chr2:179588760;179588759;179588758
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: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-55
• Domain position: 33
• Structural Position: 47
• Q(SASA): 0.215
• 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
A/V	rs374625641	0.406	0.473	N	0.535	0.216	None	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
A/V	rs374625641	0.406	0.473	N	0.535	0.216	None	gnomAD-4.0.0	2.2583E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69876E-05	0	4.97183E-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
A/C	0.5306	ambiguous	0.5317	ambiguous	-0.518	Destabilizing	0.995	D	0.596	neutral	None	None	None	None	N
A/D	0.2124	likely_benign	0.2019	benign	-1.495	Destabilizing	0.473	N	0.558	neutral	D	0.524303988	None	None	N
A/E	0.1912	likely_benign	0.1923	benign	-1.432	Destabilizing	0.329	N	0.525	neutral	None	None	None	None	N
A/F	0.3232	likely_benign	0.2851	benign	-0.766	Destabilizing	0.893	D	0.555	neutral	None	None	None	None	N
A/G	0.1395	likely_benign	0.1327	benign	-1.168	Destabilizing	0.27	N	0.508	neutral	N	0.480110494	None	None	N
A/H	0.4359	ambiguous	0.4161	ambiguous	-1.527	Destabilizing	0.017	N	0.542	neutral	None	None	None	None	N
A/I	0.2621	likely_benign	0.2343	benign	0.004	Stabilizing	0.543	D	0.577	neutral	None	None	None	None	N
A/K	0.4655	ambiguous	0.4396	ambiguous	-1.095	Destabilizing	0.543	D	0.54	neutral	None	None	None	None	N
A/L	0.2013	likely_benign	0.1848	benign	0.004	Stabilizing	0.007	N	0.454	neutral	None	None	None	None	N
A/M	0.2496	likely_benign	0.2195	benign	0.072	Stabilizing	0.893	D	0.571	neutral	None	None	None	None	N
A/N	0.2289	likely_benign	0.2115	benign	-0.939	Destabilizing	0.007	N	0.542	neutral	None	None	None	None	N
A/P	0.8458	likely_pathogenic	0.832	pathogenic	-0.229	Destabilizing	0.927	D	0.593	neutral	N	0.499152683	None	None	N
A/Q	0.2997	likely_benign	0.2935	benign	-0.969	Destabilizing	0.085	N	0.357	neutral	None	None	None	None	N
A/R	0.3736	ambiguous	0.352	ambiguous	-0.918	Destabilizing	0.704	D	0.571	neutral	None	None	None	None	N
A/S	0.0795	likely_benign	0.0782	benign	-1.273	Destabilizing	0.01	N	0.259	neutral	N	0.371091943	None	None	N
A/T	0.0798	likely_benign	0.0757	benign	-1.111	Destabilizing	0.473	N	0.519	neutral	N	0.38258116	None	None	N
A/V	0.1457	likely_benign	0.1307	benign	-0.229	Destabilizing	0.473	N	0.535	neutral	N	0.466661194	None	None	N
A/W	0.722	likely_pathogenic	0.6977	pathogenic	-1.347	Destabilizing	0.995	D	0.651	neutral	None	None	None	None	N
A/Y	0.4468	ambiguous	0.4145	ambiguous	-0.824	Destabilizing	0.893	D	0.555	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.