TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26328	79207;79208;79209	chr2:178567150;178567149;178567148	chr2:179431877;179431876;179431875
N2AB	24687	74284;74285;74286	chr2:178567150;178567149;178567148	chr2:179431877;179431876;179431875
N2A	23760	71503;71504;71505	chr2:178567150;178567149;178567148	chr2:179431877;179431876;179431875
N2B	17263	52012;52013;52014	chr2:178567150;178567149;178567148	chr2:179431877;179431876;179431875
Novex-1	17388	52387;52388;52389	chr2:178567150;178567149;178567148	chr2:179431877;179431876;179431875
Novex-2	17455	52588;52589;52590	chr2:178567150;178567149;178567148	chr2:179431877;179431876;179431875
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: Fn3-79
• Domain position: 43
• Structural Position: 44
• Q(SASA): 0.2753
• 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/A	rs746887830	-1.154	0.999	N	0.645	0.64	0.572001775666	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
E/A	rs746887830	-1.154	0.999	N	0.645	0.64	0.572001775666	gnomAD-4.0.0	1.59186E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85951E-06	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
E/A	0.9839	likely_pathogenic	0.9842	pathogenic	-1.054	Destabilizing	0.999	D	0.645	neutral	N	0.493311381	None	None	N
E/C	0.9986	likely_pathogenic	0.9988	pathogenic	-0.58	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
E/D	0.9657	likely_pathogenic	0.9639	pathogenic	-1.325	Destabilizing	0.999	D	0.465	neutral	N	0.489468191	None	None	N
E/F	0.9996	likely_pathogenic	0.9996	pathogenic	-0.578	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
E/G	0.9854	likely_pathogenic	0.9873	pathogenic	-1.437	Destabilizing	1.0	D	0.675	neutral	N	0.49794619	None	None	N
E/H	0.9985	likely_pathogenic	0.9984	pathogenic	-0.909	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	N
E/I	0.9983	likely_pathogenic	0.9985	pathogenic	0.002	Stabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
E/K	0.9918	likely_pathogenic	0.992	pathogenic	-0.828	Destabilizing	0.999	D	0.575	neutral	D	0.524522127	None	None	N
E/L	0.9982	likely_pathogenic	0.9981	pathogenic	0.002	Stabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
E/M	0.9975	likely_pathogenic	0.9973	pathogenic	0.573	Stabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
E/N	0.9961	likely_pathogenic	0.9957	pathogenic	-1.254	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
E/P	0.9982	likely_pathogenic	0.9981	pathogenic	-0.33	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
E/Q	0.9719	likely_pathogenic	0.9726	pathogenic	-1.122	Destabilizing	1.0	D	0.619	neutral	N	0.485118173	None	None	N
E/R	0.9937	likely_pathogenic	0.9938	pathogenic	-0.596	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
E/S	0.9918	likely_pathogenic	0.9926	pathogenic	-1.648	Destabilizing	0.999	D	0.609	neutral	None	None	None	None	N
E/T	0.9979	likely_pathogenic	0.9981	pathogenic	-1.323	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
E/V	0.9951	likely_pathogenic	0.9956	pathogenic	-0.33	Destabilizing	1.0	D	0.773	deleterious	N	0.495312844	None	None	N
E/W	0.9998	likely_pathogenic	0.9998	pathogenic	-0.349	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
E/Y	0.9993	likely_pathogenic	0.9992	pathogenic	-0.319	Destabilizing	1.0	D	0.753	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.