TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30658	92197;92198;92199	chr2:178549750;178549749;178549748	chr2:179414477;179414476;179414475
N2AB	29017	87274;87275;87276	chr2:178549750;178549749;178549748	chr2:179414477;179414476;179414475
N2A	28090	84493;84494;84495	chr2:178549750;178549749;178549748	chr2:179414477;179414476;179414475
N2B	21593	65002;65003;65004	chr2:178549750;178549749;178549748	chr2:179414477;179414476;179414475
Novex-1	21718	65377;65378;65379	chr2:178549750;178549749;178549748	chr2:179414477;179414476;179414475
Novex-2	21785	65578;65579;65580	chr2:178549750;178549749;178549748	chr2:179414477;179414476;179414475
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: Fn3-111
• Domain position: 40
• Structural Position: 41
• Q(SASA): 0.2021
• 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
E/D	rs1240970665	-1.609	0.999	N	0.645	0.353	0.231231049324	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
E/D	rs1240970665	-1.609	0.999	N	0.645	0.353	0.231231049324	gnomAD-4.0.0	1.59142E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43291E-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	0.8365	likely_pathogenic	0.857	pathogenic	-1.164	Destabilizing	0.999	D	0.707	prob.neutral	D	0.538976866	None	None	N
E/C	0.9854	likely_pathogenic	0.9871	pathogenic	-0.446	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
E/D	0.8222	likely_pathogenic	0.8436	pathogenic	-1.56	Destabilizing	0.999	D	0.645	neutral	N	0.50400935	None	None	N
E/F	0.99	likely_pathogenic	0.9927	pathogenic	-0.76	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
E/G	0.8673	likely_pathogenic	0.8829	pathogenic	-1.577	Destabilizing	1.0	D	0.77	deleterious	D	0.540751292	None	None	N
E/H	0.9441	likely_pathogenic	0.95	pathogenic	-0.699	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
E/I	0.9815	likely_pathogenic	0.9843	pathogenic	0.017	Stabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
E/K	0.8671	likely_pathogenic	0.8817	pathogenic	-1.143	Destabilizing	0.999	D	0.698	prob.neutral	D	0.549230308	None	None	N
E/L	0.9653	likely_pathogenic	0.9709	pathogenic	0.017	Stabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
E/M	0.9567	likely_pathogenic	0.9632	pathogenic	0.698	Stabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
E/N	0.9512	likely_pathogenic	0.9579	pathogenic	-1.453	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
E/P	0.9996	likely_pathogenic	0.9997	pathogenic	-0.361	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
E/Q	0.3487	ambiguous	0.3818	ambiguous	-1.164	Destabilizing	1.0	D	0.745	deleterious	N	0.470216696	None	None	N
E/R	0.9009	likely_pathogenic	0.9123	pathogenic	-1.002	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
E/S	0.8123	likely_pathogenic	0.8261	pathogenic	-2.054	Highly Destabilizing	0.999	D	0.748	deleterious	None	None	None	None	N
E/T	0.9357	likely_pathogenic	0.9407	pathogenic	-1.665	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
E/V	0.9446	likely_pathogenic	0.9533	pathogenic	-0.361	Destabilizing	1.0	D	0.783	deleterious	D	0.533153969	None	None	N
E/W	0.9937	likely_pathogenic	0.9952	pathogenic	-0.812	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
E/Y	0.9813	likely_pathogenic	0.9852	pathogenic	-0.535	Destabilizing	1.0	D	0.811	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.