TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29541	88846;88847;88848	chr2:178554726;178554725;178554724	chr2:179419453;179419452;179419451
N2AB	27900	83923;83924;83925	chr2:178554726;178554725;178554724	chr2:179419453;179419452;179419451
N2A	26973	81142;81143;81144	chr2:178554726;178554725;178554724	chr2:179419453;179419452;179419451
N2B	20476	61651;61652;61653	chr2:178554726;178554725;178554724	chr2:179419453;179419452;179419451
Novex-1	20601	62026;62027;62028	chr2:178554726;178554725;178554724	chr2:179419453;179419452;179419451
Novex-2	20668	62227;62228;62229	chr2:178554726;178554725;178554724	chr2:179419453;179419452;179419451
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-103
• Domain position: 9
• Structural Position: 9
• Q(SASA): 0.1762
• 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	rs768292510	-2.519	0.939	N	0.742	0.424	0.544825121038	gnomAD-2.1.1	2.14E-05	None	None	None	None	N	None	4.13E-05	0	None	0	5.12E-05	None	0	None	0	2.34E-05	1.40449E-04
I/T	rs768292510	-2.519	0.939	N	0.742	0.424	0.544825121038	gnomAD-3.1.2	5.26E-05	None	None	None	None	N	None	9.65E-05	0	0	0	1.92604E-04	None	0	0	4.41E-05	0	0
I/T	rs768292510	-2.519	0.939	N	0.742	0.424	0.544825121038	gnomAD-4.0.0	3.34625E-05	None	None	None	None	N	None	6.67254E-05	1.66728E-05	None	3.37792E-05	6.6836E-05	None	0	1.64582E-04	3.22078E-05	1.09842E-05	6.40451E-05
I/V	rs780639603	-1.172	0.02	N	0.207	0.088	0.222439326576	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	8.89E-06	0
I/V	rs780639603	-1.172	0.02	N	0.207	0.088	0.222439326576	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	2.41E-05	2.61952E-04	0	0	0	None	0	0	0	0	0
I/V	rs780639603	-1.172	0.02	N	0.207	0.088	0.222439326576	gnomAD-4.0.0	1.40892E-05	None	None	None	None	N	None	1.68725E-05	6.77713E-05	None	0	0	None	4.70662E-05	0	2.39284E-06	2.68183E-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
I/A	0.5671	likely_pathogenic	0.6099	pathogenic	-2.295	Highly Destabilizing	0.91	D	0.654	neutral	None	None	None	None	N
I/C	0.8902	likely_pathogenic	0.9134	pathogenic	-1.518	Destabilizing	0.999	D	0.674	neutral	None	None	None	None	N
I/D	0.9938	likely_pathogenic	0.9946	pathogenic	-2.71	Highly Destabilizing	0.998	D	0.801	deleterious	None	None	None	None	N
I/E	0.9824	likely_pathogenic	0.9849	pathogenic	-2.422	Highly Destabilizing	0.993	D	0.8	deleterious	None	None	None	None	N
I/F	0.4219	ambiguous	0.5009	ambiguous	-1.215	Destabilizing	0.982	D	0.777	deleterious	N	0.514478491	None	None	N
I/G	0.9558	likely_pathogenic	0.9653	pathogenic	-2.893	Highly Destabilizing	0.993	D	0.805	deleterious	None	None	None	None	N
I/H	0.9841	likely_pathogenic	0.9881	pathogenic	-2.549	Highly Destabilizing	0.999	D	0.76	deleterious	None	None	None	None	N
I/K	0.9725	likely_pathogenic	0.9768	pathogenic	-1.642	Destabilizing	0.993	D	0.798	deleterious	None	None	None	None	N
I/L	0.0907	likely_benign	0.1005	benign	-0.538	Destabilizing	0.58	D	0.496	neutral	N	0.436430634	None	None	N
I/M	0.1267	likely_benign	0.1415	benign	-0.649	Destabilizing	0.991	D	0.707	prob.neutral	N	0.515171925	None	None	N
I/N	0.9545	likely_pathogenic	0.9596	pathogenic	-2.133	Highly Destabilizing	0.997	D	0.795	deleterious	N	0.499147505	None	None	N
I/P	0.8787	likely_pathogenic	0.9033	pathogenic	-1.107	Destabilizing	0.998	D	0.794	deleterious	None	None	None	None	N
I/Q	0.9686	likely_pathogenic	0.9738	pathogenic	-1.859	Destabilizing	0.998	D	0.794	deleterious	None	None	None	None	N
I/R	0.9586	likely_pathogenic	0.9667	pathogenic	-1.653	Destabilizing	0.993	D	0.801	deleterious	None	None	None	None	N
I/S	0.8833	likely_pathogenic	0.8945	pathogenic	-2.796	Highly Destabilizing	0.991	D	0.773	deleterious	N	0.48753771	None	None	N
I/T	0.6071	likely_pathogenic	0.6695	pathogenic	-2.348	Highly Destabilizing	0.939	D	0.742	deleterious	N	0.521444536	None	None	N
I/V	0.0687	likely_benign	0.0739	benign	-1.107	Destabilizing	0.02	N	0.207	neutral	N	0.434358695	None	None	N
I/W	0.974	likely_pathogenic	0.9829	pathogenic	-1.665	Destabilizing	0.999	D	0.734	prob.delet.	None	None	None	None	N
I/Y	0.9444	likely_pathogenic	0.9583	pathogenic	-1.334	Destabilizing	0.993	D	0.721	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.