TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33017	99274;99275;99276	chr2:178538780;178538779;178538778	chr2:179403507;179403506;179403505
N2AB	31376	94351;94352;94353	chr2:178538780;178538779;178538778	chr2:179403507;179403506;179403505
N2A	30449	91570;91571;91572	chr2:178538780;178538779;178538778	chr2:179403507;179403506;179403505
N2B	23952	72079;72080;72081	chr2:178538780;178538779;178538778	chr2:179403507;179403506;179403505
Novex-1	24077	72454;72455;72456	chr2:178538780;178538779;178538778	chr2:179403507;179403506;179403505
Novex-2	24144	72655;72656;72657	chr2:178538780;178538779;178538778	chr2:179403507;179403506;179403505
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Fn3-129
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.1439
• 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
L/Q	rs1300155629	-2.332	0.997	D	0.874	0.672	0.857699135556	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
L/Q	rs1300155629	-2.332	0.997	D	0.874	0.672	0.857699135556	gnomAD-4.0.0	4.77487E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	4.29984E-05	0
L/R	None	None	0.997	D	0.857	0.713	0.870081891428	gnomAD-4.0.0	1.59162E-06	None	None	None	None	N	None	0	0	None	0	2.77316E-05	None	0	0	0	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
L/A	0.8994	likely_pathogenic	0.9043	pathogenic	-2.733	Highly Destabilizing	0.953	D	0.685	prob.neutral	None	None	None	None	N
L/C	0.8667	likely_pathogenic	0.8733	pathogenic	-1.73	Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	N
L/D	0.9994	likely_pathogenic	0.9995	pathogenic	-3.531	Highly Destabilizing	0.998	D	0.891	deleterious	None	None	None	None	N
L/E	0.9942	likely_pathogenic	0.9951	pathogenic	-3.208	Highly Destabilizing	0.998	D	0.888	deleterious	None	None	None	None	N
L/F	0.3577	ambiguous	0.4416	ambiguous	-1.724	Destabilizing	0.986	D	0.668	neutral	None	None	None	None	N
L/G	0.9877	likely_pathogenic	0.9902	pathogenic	-3.315	Highly Destabilizing	0.998	D	0.883	deleterious	None	None	None	None	N
L/H	0.9817	likely_pathogenic	0.9854	pathogenic	-3.103	Highly Destabilizing	0.999	D	0.869	deleterious	None	None	None	None	N
L/I	0.0902	likely_benign	0.0939	benign	-0.966	Destabilizing	0.02	N	0.253	neutral	N	0.508366169	None	None	N
L/K	0.9912	likely_pathogenic	0.9923	pathogenic	-2.251	Highly Destabilizing	0.993	D	0.847	deleterious	None	None	None	None	N
L/M	0.1769	likely_benign	0.2012	benign	-1.053	Destabilizing	0.986	D	0.629	neutral	None	None	None	None	N
L/N	0.9953	likely_pathogenic	0.9961	pathogenic	-3.041	Highly Destabilizing	0.998	D	0.895	deleterious	None	None	None	None	N
L/P	0.9965	likely_pathogenic	0.9975	pathogenic	-1.549	Destabilizing	0.997	D	0.897	deleterious	D	0.538231121	None	None	N
L/Q	0.9737	likely_pathogenic	0.9782	pathogenic	-2.648	Highly Destabilizing	0.997	D	0.874	deleterious	D	0.560943732	None	None	N
L/R	0.9824	likely_pathogenic	0.9856	pathogenic	-2.355	Highly Destabilizing	0.997	D	0.857	deleterious	D	0.560943732	None	None	N
L/S	0.9838	likely_pathogenic	0.986	pathogenic	-3.471	Highly Destabilizing	0.993	D	0.818	deleterious	None	None	None	None	N
L/T	0.9348	likely_pathogenic	0.9372	pathogenic	-2.99	Highly Destabilizing	0.986	D	0.737	prob.delet.	None	None	None	None	N
L/V	0.1243	likely_benign	0.1305	benign	-1.549	Destabilizing	0.76	D	0.425	neutral	N	0.50693923	None	None	N
L/W	0.9187	likely_pathogenic	0.9453	pathogenic	-2.113	Highly Destabilizing	0.999	D	0.805	deleterious	None	None	None	None	N
L/Y	0.9304	likely_pathogenic	0.9489	pathogenic	-1.929	Destabilizing	0.998	D	0.711	prob.delet.	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.