TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3257	9994;9995;9996	chr2:178764746;178764745;178764744	chr2:179629473;179629472;179629471
N2AB	3257	9994;9995;9996	chr2:178764746;178764745;178764744	chr2:179629473;179629472;179629471
N2A	3257	9994;9995;9996	chr2:178764746;178764745;178764744	chr2:179629473;179629472;179629471
N2B	3211	9856;9857;9858	chr2:178764746;178764745;178764744	chr2:179629473;179629472;179629471
Novex-1	3211	9856;9857;9858	chr2:178764746;178764745;178764744	chr2:179629473;179629472;179629471
Novex-2	3211	9856;9857;9858	chr2:178764746;178764745;178764744	chr2:179629473;179629472;179629471
Novex-3	3257	9994;9995;9996	chr2:178764746;178764745;178764744	chr2:179629473;179629472;179629471

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGC
• RefSeq wild type template codon: GCG
• Domain: Ig-23
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.5037
• 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
R/C	rs374521620	-0.522	1.0	D	0.757	0.801	0.800107164582	gnomAD-2.1.1	3.59E-05	None	None	None	None	N	None	0	1.44642E-04	None	0	0	None	0	None	0	2.65E-05	1.63613E-04
R/C	rs374521620	-0.522	1.0	D	0.757	0.801	0.800107164582	gnomAD-4.0.0	6.15723E-06	None	None	None	None	N	None	0	1.11822E-04	None	0	0	None	0	0	1.79865E-06	1.15942E-05	1.6564E-05
R/G	None	None	1.0	D	0.699	0.846	0.781155158808	gnomAD-4.0.0	6.84137E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99323E-07	0	0
R/H	rs535876380	-1.214	1.0	N	0.746	0.672	0.446510307777	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	6.15E-05	8.68E-05	None	0	0	None	0	None	0	3.53E-05	0
R/H	rs535876380	-1.214	1.0	N	0.746	0.672	0.446510307777	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	2.41E-05	6.55E-05	0	0	0	None	0	0	1.47E-05	2.07211E-04	0
R/H	rs535876380	-1.214	1.0	N	0.746	0.672	0.446510307777	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	1.4E-03	None	None	0	0	None	None	None	0	None
R/H	rs535876380	-1.214	1.0	N	0.746	0.672	0.446510307777	gnomAD-4.0.0	7.06306E-05	None	None	None	None	N	None	1.3328E-05	6.66511E-05	None	0	0	None	0	0	8.98313E-05	1.09801E-05	3.20061E-05
R/S	rs374521620	-0.69	1.0	N	0.729	0.782	None	gnomAD-2.1.1	1.99E-05	None	None	None	None	N	None	0	5.79E-05	None	0	0	None	0	None	0	2.65E-05	0
R/S	rs374521620	-0.69	1.0	N	0.729	0.782	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	1.30941E-04	0	0	0	None	0	0	1.47E-05	0	0
R/S	rs374521620	-0.69	1.0	N	0.729	0.782	None	gnomAD-4.0.0	1.30125E-05	None	None	None	None	N	None	0	1.0002E-04	None	0	0	None	0	0	1.27121E-05	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
R/A	0.8654	likely_pathogenic	0.9352	pathogenic	-0.103	Destabilizing	0.999	D	0.633	neutral	None	None	None	None	N
R/C	0.468	ambiguous	0.6852	pathogenic	-0.244	Destabilizing	1.0	D	0.757	deleterious	D	0.614298754	None	None	N
R/D	0.9653	likely_pathogenic	0.9849	pathogenic	-0.024	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
R/E	0.7779	likely_pathogenic	0.8758	pathogenic	0.078	Stabilizing	0.999	D	0.638	neutral	None	None	None	None	N
R/F	0.91	likely_pathogenic	0.9594	pathogenic	-0.152	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
R/G	0.8364	likely_pathogenic	0.9275	pathogenic	-0.356	Destabilizing	1.0	D	0.699	prob.neutral	D	0.665218711	None	None	N
R/H	0.237	likely_benign	0.4263	ambiguous	-0.881	Destabilizing	1.0	D	0.746	deleterious	N	0.513096016	None	None	N
R/I	0.7059	likely_pathogenic	0.8096	pathogenic	0.544	Stabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
R/K	0.2878	likely_benign	0.4045	ambiguous	-0.148	Destabilizing	0.998	D	0.519	neutral	None	None	None	None	N
R/L	0.6494	likely_pathogenic	0.7819	pathogenic	0.544	Stabilizing	1.0	D	0.699	prob.neutral	N	0.518441285	None	None	N
R/M	0.7995	likely_pathogenic	0.8904	pathogenic	0.004	Stabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
R/N	0.9178	likely_pathogenic	0.9638	pathogenic	0.064	Stabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
R/P	0.9779	likely_pathogenic	0.9914	pathogenic	0.35	Stabilizing	1.0	D	0.715	prob.delet.	D	0.704105458	None	None	N
R/Q	0.2276	likely_benign	0.3996	ambiguous	0.012	Stabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
R/S	0.8467	likely_pathogenic	0.9287	pathogenic	-0.36	Destabilizing	1.0	D	0.729	prob.delet.	N	0.518302105	None	None	N
R/T	0.6987	likely_pathogenic	0.8408	pathogenic	-0.095	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
R/V	0.7218	likely_pathogenic	0.8188	pathogenic	0.35	Stabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
R/W	0.5275	ambiguous	0.7388	pathogenic	-0.119	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
R/Y	0.7564	likely_pathogenic	0.8927	pathogenic	0.267	Stabilizing	1.0	D	0.738	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.