TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27804	83635;83636;83637	chr2:178562722;178562721;178562720	chr2:179427449;179427448;179427447
N2AB	26163	78712;78713;78714	chr2:178562722;178562721;178562720	chr2:179427449;179427448;179427447
N2A	25236	75931;75932;75933	chr2:178562722;178562721;178562720	chr2:179427449;179427448;179427447
N2B	18739	56440;56441;56442	chr2:178562722;178562721;178562720	chr2:179427449;179427448;179427447
Novex-1	18864	56815;56816;56817	chr2:178562722;178562721;178562720	chr2:179427449;179427448;179427447
Novex-2	18931	57016;57017;57018	chr2:178562722;178562721;178562720	chr2:179427449;179427448;179427447
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-90
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.1341
• 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
E/K	rs759095633	-1.614	1.0	N	0.685	0.457	0.444706120422	gnomAD-2.1.1	2.51E-05	None	None	None	None	N	None	1.31148E-04	0	None	0	5.75E-05	None	0	None	0	1.82E-05	1.75254E-04
E/K	rs759095633	-1.614	1.0	N	0.685	0.457	0.444706120422	gnomAD-4.0.0	1.24416E-05	None	None	None	None	N	None	1.23069E-04	0	None	0	2.53254E-05	None	1.88708E-05	0	1.08546E-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
E/A	0.9174	likely_pathogenic	0.8914	pathogenic	-1.589	Destabilizing	1.0	D	0.682	prob.neutral	D	0.525810135	None	None	N
E/C	0.9927	likely_pathogenic	0.9924	pathogenic	-0.67	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
E/D	0.8691	likely_pathogenic	0.7985	pathogenic	-1.697	Destabilizing	0.998	D	0.662	neutral	N	0.471915444	None	None	N
E/F	0.9976	likely_pathogenic	0.9977	pathogenic	-1.267	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
E/G	0.9417	likely_pathogenic	0.9298	pathogenic	-1.986	Destabilizing	1.0	D	0.739	prob.delet.	D	0.538940867	None	None	N
E/H	0.9889	likely_pathogenic	0.9877	pathogenic	-1.06	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
E/I	0.9893	likely_pathogenic	0.9881	pathogenic	-0.444	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
E/K	0.9689	likely_pathogenic	0.9647	pathogenic	-1.332	Destabilizing	1.0	D	0.685	prob.neutral	N	0.498867562	None	None	N
E/L	0.9846	likely_pathogenic	0.9833	pathogenic	-0.444	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
E/M	0.9754	likely_pathogenic	0.9722	pathogenic	0.293	Stabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
E/N	0.9787	likely_pathogenic	0.9652	pathogenic	-1.593	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
E/P	0.9998	likely_pathogenic	0.9998	pathogenic	-0.812	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
E/Q	0.5457	ambiguous	0.5212	ambiguous	-1.311	Destabilizing	1.0	D	0.764	deleterious	N	0.468077102	None	None	N
E/R	0.9768	likely_pathogenic	0.9751	pathogenic	-1.161	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
E/S	0.9202	likely_pathogenic	0.8895	pathogenic	-2.247	Highly Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
E/T	0.9767	likely_pathogenic	0.9644	pathogenic	-1.861	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
E/V	0.9692	likely_pathogenic	0.964	pathogenic	-0.812	Destabilizing	1.0	D	0.729	prob.delet.	N	0.497110043	None	None	N
E/W	0.9991	likely_pathogenic	0.9993	pathogenic	-1.299	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
E/Y	0.9961	likely_pathogenic	0.9957	pathogenic	-1.038	Destabilizing	1.0	D	0.763	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.