TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19557	58894;58895;58896	chr2:178593631;178593630;178593629	chr2:179458358;179458357;179458356
N2AB	17916	53971;53972;53973	chr2:178593631;178593630;178593629	chr2:179458358;179458357;179458356
N2A	16989	51190;51191;51192	chr2:178593631;178593630;178593629	chr2:179458358;179458357;179458356
N2B	10492	31699;31700;31701	chr2:178593631;178593630;178593629	chr2:179458358;179458357;179458356
Novex-1	10617	32074;32075;32076	chr2:178593631;178593630;178593629	chr2:179458358;179458357;179458356
Novex-2	10684	32275;32276;32277	chr2:178593631;178593630;178593629	chr2:179458358;179458357;179458356
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: Fn3-29
• Domain position: 79
• Structural Position: 111
• Q(SASA): 0.2988
• Predicted PPI site: I

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	None	None	0.956	N	0.513	0.282	0.34854441366	gnomAD-4.0.0	2.40065E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.31251E-06	6.07533E-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
E/A	0.5757	likely_pathogenic	0.5142	ambiguous	-0.614	Destabilizing	0.978	D	0.571	neutral	N	0.4690117	None	None	I
E/C	0.9667	likely_pathogenic	0.9563	pathogenic	-0.352	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	I
E/D	0.9313	likely_pathogenic	0.9146	pathogenic	-1.289	Destabilizing	0.948	D	0.483	neutral	N	0.491612633	None	None	I
E/F	0.9885	likely_pathogenic	0.9811	pathogenic	-0.868	Destabilizing	0.999	D	0.807	deleterious	None	None	None	None	I
E/G	0.771	likely_pathogenic	0.7198	pathogenic	-0.922	Destabilizing	0.989	D	0.689	prob.neutral	N	0.496385573	None	None	I
E/H	0.9555	likely_pathogenic	0.9415	pathogenic	-1.171	Destabilizing	0.998	D	0.6	neutral	None	None	None	None	I
E/I	0.8084	likely_pathogenic	0.728	pathogenic	0.204	Stabilizing	0.999	D	0.815	deleterious	None	None	None	None	I
E/K	0.5557	ambiguous	0.4938	ambiguous	-0.473	Destabilizing	0.956	D	0.513	neutral	N	0.517190723	None	None	I
E/L	0.9343	likely_pathogenic	0.9018	pathogenic	0.204	Stabilizing	0.995	D	0.759	deleterious	None	None	None	None	I
E/M	0.8364	likely_pathogenic	0.7749	pathogenic	0.687	Stabilizing	1.0	D	0.778	deleterious	None	None	None	None	I
E/N	0.9368	likely_pathogenic	0.916	pathogenic	-0.752	Destabilizing	0.998	D	0.587	neutral	None	None	None	None	I
E/P	0.9985	likely_pathogenic	0.9983	pathogenic	-0.047	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	I
E/Q	0.2486	likely_benign	0.2191	benign	-0.665	Destabilizing	0.63	D	0.192	neutral	N	0.472226437	None	None	I
E/R	0.7142	likely_pathogenic	0.6721	pathogenic	-0.503	Destabilizing	0.983	D	0.553	neutral	None	None	None	None	I
E/S	0.7597	likely_pathogenic	0.7097	pathogenic	-1.096	Destabilizing	0.983	D	0.497	neutral	None	None	None	None	I
E/T	0.7623	likely_pathogenic	0.7068	pathogenic	-0.829	Destabilizing	0.992	D	0.69	prob.neutral	None	None	None	None	I
E/V	0.5396	ambiguous	0.4439	ambiguous	-0.047	Destabilizing	0.997	D	0.743	deleterious	N	0.463387949	None	None	I
E/W	0.9971	likely_pathogenic	0.9957	pathogenic	-0.94	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	I
E/Y	0.9845	likely_pathogenic	0.9776	pathogenic	-0.66	Destabilizing	0.999	D	0.805	deleterious	None	None	None	None	I

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.