TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19106	57541;57542;57543	chr2:178597766;178597765;178597764	chr2:179462493;179462492;179462491
N2AB	17465	52618;52619;52620	chr2:178597766;178597765;178597764	chr2:179462493;179462492;179462491
N2A	16538	49837;49838;49839	chr2:178597766;178597765;178597764	chr2:179462493;179462492;179462491
N2B	10041	30346;30347;30348	chr2:178597766;178597765;178597764	chr2:179462493;179462492;179462491
Novex-1	10166	30721;30722;30723	chr2:178597766;178597765;178597764	chr2:179462493;179462492;179462491
Novex-2	10233	30922;30923;30924	chr2:178597766;178597765;178597764	chr2:179462493;179462492;179462491
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-117
• Domain position: 12
• Structural Position: 23
• Q(SASA): 0.4373
• 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
A/T	rs754573037	-0.637	1.0	N	0.693	0.371	0.358948522604	gnomAD-2.1.1	1.61E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	3.57E-05	0
A/T	rs754573037	-0.637	1.0	N	0.693	0.371	0.358948522604	gnomAD-4.0.0	1.27402E-05	None	None	None	None	I	None	0	2.28948E-05	None	0	0	None	0	0	2.00189E-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
A/C	0.6216	likely_pathogenic	0.6765	pathogenic	-0.618	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
A/D	0.9072	likely_pathogenic	0.9478	pathogenic	-1.053	Destabilizing	1.0	D	0.787	deleterious	N	0.472114529	None	None	I
A/E	0.8111	likely_pathogenic	0.8778	pathogenic	-1.21	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
A/F	0.827	likely_pathogenic	0.9131	pathogenic	-1.198	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
A/G	0.4688	ambiguous	0.6028	pathogenic	-0.616	Destabilizing	1.0	D	0.525	neutral	N	0.501828579	None	None	I
A/H	0.7692	likely_pathogenic	0.8542	pathogenic	-0.749	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
A/I	0.6466	likely_pathogenic	0.7339	pathogenic	-0.496	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	I
A/K	0.7915	likely_pathogenic	0.8717	pathogenic	-0.866	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	I
A/L	0.6642	likely_pathogenic	0.7213	pathogenic	-0.496	Destabilizing	1.0	D	0.649	neutral	None	None	None	None	I
A/M	0.6086	likely_pathogenic	0.7059	pathogenic	-0.241	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	I
A/N	0.705	likely_pathogenic	0.7904	pathogenic	-0.424	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
A/P	0.9563	likely_pathogenic	0.973	pathogenic	-0.473	Destabilizing	1.0	D	0.717	prob.delet.	N	0.464517205	None	None	I
A/Q	0.6487	likely_pathogenic	0.7115	pathogenic	-0.779	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
A/R	0.661	likely_pathogenic	0.7432	pathogenic	-0.311	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	I
A/S	0.1398	likely_benign	0.1819	benign	-0.574	Destabilizing	1.0	D	0.547	neutral	N	0.456376904	None	None	I
A/T	0.2724	likely_benign	0.3405	ambiguous	-0.667	Destabilizing	1.0	D	0.693	prob.neutral	N	0.515430136	None	None	I
A/V	0.2907	likely_benign	0.3736	ambiguous	-0.473	Destabilizing	1.0	D	0.614	neutral	N	0.506077147	None	None	I
A/W	0.9671	likely_pathogenic	0.9824	pathogenic	-1.352	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
A/Y	0.8803	likely_pathogenic	0.9375	pathogenic	-1.01	Destabilizing	1.0	D	0.809	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.