TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5242	15949;15950;15951	chr2:178733665;178733664;178733663	chr2:179598392;179598391;179598390
N2AB	4925	14998;14999;15000	chr2:178733665;178733664;178733663	chr2:179598392;179598391;179598390
N2A	3998	12217;12218;12219	chr2:178733665;178733664;178733663	chr2:179598392;179598391;179598390
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: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-35
• Domain position: 75
• Structural Position: 158
• Q(SASA): 0.1005
• 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/T	rs763604864	-1.818	0.996	D	0.696	0.8	0.611371111137	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
A/T	rs763604864	-1.818	0.996	D	0.696	0.8	0.611371111137	gnomAD-4.0.0	1.59333E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43365E-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
A/C	0.7825	likely_pathogenic	0.7941	pathogenic	-1.511	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
A/D	0.9976	likely_pathogenic	0.998	pathogenic	-2.206	Highly Destabilizing	1.0	D	0.865	deleterious	D	0.827716354	None	None	N
A/E	0.9909	likely_pathogenic	0.9924	pathogenic	-2.064	Highly Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
A/F	0.9372	likely_pathogenic	0.9391	pathogenic	-0.895	Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
A/G	0.5387	ambiguous	0.5719	pathogenic	-1.758	Destabilizing	0.999	D	0.624	neutral	D	0.736268177	None	None	N
A/H	0.9965	likely_pathogenic	0.9968	pathogenic	-1.897	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
A/I	0.4613	ambiguous	0.5211	ambiguous	-0.188	Destabilizing	0.994	D	0.759	deleterious	None	None	None	None	N
A/K	0.9979	likely_pathogenic	0.9985	pathogenic	-1.39	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
A/L	0.5035	ambiguous	0.5584	ambiguous	-0.188	Destabilizing	0.994	D	0.697	prob.neutral	None	None	None	None	N
A/M	0.74	likely_pathogenic	0.7761	pathogenic	-0.459	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
A/N	0.9936	likely_pathogenic	0.9941	pathogenic	-1.532	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
A/P	0.9889	likely_pathogenic	0.9909	pathogenic	-0.524	Destabilizing	1.0	D	0.877	deleterious	D	0.72123373	None	None	N
A/Q	0.9868	likely_pathogenic	0.9887	pathogenic	-1.455	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
A/R	0.9908	likely_pathogenic	0.9928	pathogenic	-1.318	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
A/S	0.5166	ambiguous	0.5027	ambiguous	-2.011	Highly Destabilizing	0.998	D	0.631	neutral	D	0.74639517	None	None	N
A/T	0.5221	ambiguous	0.5344	ambiguous	-1.748	Destabilizing	0.996	D	0.696	prob.neutral	D	0.758803426	None	None	N
A/V	0.2083	likely_benign	0.2338	benign	-0.524	Destabilizing	0.884	D	0.399	neutral	D	0.529581264	None	None	N
A/W	0.9961	likely_pathogenic	0.9968	pathogenic	-1.477	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
A/Y	0.989	likely_pathogenic	0.99	pathogenic	-1.011	Destabilizing	1.0	D	0.894	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.