TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33651	101176;101177;101178	chr2:178535664;178535663;178535662	chr2:179400391;179400390;179400389
N2AB	32010	96253;96254;96255	chr2:178535664;178535663;178535662	chr2:179400391;179400390;179400389
N2A	31083	93472;93473;93474	chr2:178535664;178535663;178535662	chr2:179400391;179400390;179400389
N2B	24586	73981;73982;73983	chr2:178535664;178535663;178535662	chr2:179400391;179400390;179400389
Novex-1	24711	74356;74357;74358	chr2:178535664;178535663;178535662	chr2:179400391;179400390;179400389
Novex-2	24778	74557;74558;74559	chr2:178535664;178535663;178535662	chr2:179400391;179400390;179400389
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-159
• Domain position: 56
• Structural Position: 136
• Q(SASA): 0.0767
• 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
T/I	rs1559050637	None	1.0	N	0.855	0.542	0.326616659874	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
T/I	rs1559050637	None	1.0	N	0.855	0.542	0.326616659874	gnomAD-4.0.0	2.73685E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59787E-06	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
T/A	0.724	likely_pathogenic	0.4773	ambiguous	-1.214	Destabilizing	0.999	D	0.613	neutral	N	0.467558831	None	None	N
T/C	0.9214	likely_pathogenic	0.8011	pathogenic	-0.622	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
T/D	0.9987	likely_pathogenic	0.9951	pathogenic	-2.156	Highly Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
T/E	0.999	likely_pathogenic	0.9958	pathogenic	-1.833	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
T/F	0.9969	likely_pathogenic	0.983	pathogenic	-0.8	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
T/G	0.956	likely_pathogenic	0.8849	pathogenic	-1.652	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
T/H	0.994	likely_pathogenic	0.9726	pathogenic	-1.48	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
T/I	0.9873	likely_pathogenic	0.9553	pathogenic	0.003	Stabilizing	1.0	D	0.855	deleterious	N	0.47131438	None	None	N
T/K	0.9989	likely_pathogenic	0.9951	pathogenic	-0.057	Destabilizing	1.0	D	0.807	deleterious	N	0.5052905	None	None	N
T/L	0.9513	likely_pathogenic	0.8597	pathogenic	0.003	Stabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
T/M	0.9483	likely_pathogenic	0.8249	pathogenic	-0.455	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
T/N	0.9869	likely_pathogenic	0.9546	pathogenic	-1.202	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
T/P	0.9908	likely_pathogenic	0.9718	pathogenic	-0.381	Destabilizing	1.0	D	0.864	deleterious	N	0.472328339	None	None	N
T/Q	0.9958	likely_pathogenic	0.9831	pathogenic	-0.691	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
T/R	0.9975	likely_pathogenic	0.9896	pathogenic	-0.648	Destabilizing	1.0	D	0.862	deleterious	N	0.491937201	None	None	N
T/S	0.7113	likely_pathogenic	0.5101	ambiguous	-1.323	Destabilizing	0.998	D	0.596	neutral	N	0.460574144	None	None	N
T/V	0.9177	likely_pathogenic	0.8284	pathogenic	-0.381	Destabilizing	1.0	D	0.605	neutral	None	None	None	None	N
T/W	0.9995	likely_pathogenic	0.9972	pathogenic	-1.075	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
T/Y	0.9983	likely_pathogenic	0.9883	pathogenic	-0.651	Destabilizing	1.0	D	0.878	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.