TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19521	58786;58787;58788	chr2:178593739;178593738;178593737	chr2:179458466;179458465;179458464
N2AB	17880	53863;53864;53865	chr2:178593739;178593738;178593737	chr2:179458466;179458465;179458464
N2A	16953	51082;51083;51084	chr2:178593739;178593738;178593737	chr2:179458466;179458465;179458464
N2B	10456	31591;31592;31593	chr2:178593739;178593738;178593737	chr2:179458466;179458465;179458464
Novex-1	10581	31966;31967;31968	chr2:178593739;178593738;178593737	chr2:179458466;179458465;179458464
Novex-2	10648	32167;32168;32169	chr2:178593739;178593738;178593737	chr2:179458466;179458465;179458464
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: 43
• Structural Position: 44
• Q(SASA): 0.2945
• 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	rs1156295835	-1.244	0.001	N	0.083	0.039	0.0611884634855	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	0	None	9.97E-05	0	None	0	None	0	8.91E-06	0
E/D	rs1156295835	-1.244	0.001	N	0.083	0.039	0.0611884634855	gnomAD-4.0.0	3.18433E-06	None	None	None	None	N	None	0	0	None	4.77008E-05	0	None	0	0	2.8593E-06	0	0
E/G	rs543122164	-1.112	0.549	N	0.456	0.32	0.482209950775	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.61E-05	None	0	None	0	0	0
E/G	rs543122164	-1.112	0.549	N	0.456	0.32	0.482209950775	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.94175E-04	None	0	0	0	0	0
E/G	rs543122164	-1.112	0.549	N	0.456	0.32	0.482209950775	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	1E-03	0	None	None	None	0	None
E/G	rs543122164	-1.112	0.549	N	0.456	0.32	0.482209950775	gnomAD-4.0.0	2.56333E-06	None	None	None	None	N	None	0	0	None	0	4.86997E-05	None	0	0	0	0	0
E/K	rs746319976	-0.338	0.549	N	0.381	0.223	0.394384168047	gnomAD-2.1.1	2.02E-05	None	None	None	None	N	None	0	1.45214E-04	None	0	0	None	0	None	0	0	0
E/K	rs746319976	-0.338	0.549	N	0.381	0.223	0.394384168047	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	1.31113E-04	0	0	0	None	0	0	0	0	0
E/K	rs746319976	-0.338	0.549	N	0.381	0.223	0.394384168047	gnomAD-4.0.0	5.579E-06	None	None	None	None	N	None	0	1.5017E-04	None	0	0	None	0	0	0	0	0
E/V	rs543122164	0.553	0.896	N	0.457	0.388	0.640367608718	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	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
E/A	0.3751	ambiguous	0.2	benign	-0.663	Destabilizing	0.549	D	0.399	neutral	N	0.470105018	None	None	N
E/C	0.9547	likely_pathogenic	0.8839	pathogenic	-0.529	Destabilizing	0.992	D	0.534	neutral	None	None	None	None	N
E/D	0.179	likely_benign	0.1259	benign	-1.226	Destabilizing	0.001	N	0.083	neutral	N	0.419704248	None	None	N
E/F	0.9413	likely_pathogenic	0.857	pathogenic	0.136	Stabilizing	0.972	D	0.523	neutral	None	None	None	None	N
E/G	0.5183	ambiguous	0.325	benign	-1.064	Destabilizing	0.549	D	0.456	neutral	N	0.472435649	None	None	N
E/H	0.8693	likely_pathogenic	0.7289	pathogenic	-0.13	Destabilizing	0.972	D	0.404	neutral	None	None	None	None	N
E/I	0.6425	likely_pathogenic	0.4249	ambiguous	0.441	Stabilizing	0.92	D	0.539	neutral	None	None	None	None	N
E/K	0.7126	likely_pathogenic	0.5065	ambiguous	-0.763	Destabilizing	0.549	D	0.381	neutral	N	0.494892653	None	None	N
E/L	0.7017	likely_pathogenic	0.4852	ambiguous	0.441	Stabilizing	0.92	D	0.481	neutral	None	None	None	None	N
E/M	0.7405	likely_pathogenic	0.545	ambiguous	0.782	Stabilizing	0.992	D	0.476	neutral	None	None	None	None	N
E/N	0.6023	likely_pathogenic	0.3943	ambiguous	-1.312	Destabilizing	0.447	N	0.356	neutral	None	None	None	None	N
E/P	0.8182	likely_pathogenic	0.6448	pathogenic	0.095	Stabilizing	0.766	D	0.377	neutral	None	None	None	None	N
E/Q	0.4744	ambiguous	0.3046	benign	-1.12	Destabilizing	0.549	D	0.398	neutral	N	0.510246108	None	None	N
E/R	0.8009	likely_pathogenic	0.6337	pathogenic	-0.392	Destabilizing	0.92	D	0.387	neutral	None	None	None	None	N
E/S	0.5689	likely_pathogenic	0.3312	benign	-1.625	Destabilizing	0.25	N	0.387	neutral	None	None	None	None	N
E/T	0.6078	likely_pathogenic	0.3833	ambiguous	-1.289	Destabilizing	0.617	D	0.345	neutral	None	None	None	None	N
E/V	0.4538	ambiguous	0.2564	benign	0.095	Stabilizing	0.896	D	0.457	neutral	N	0.475398164	None	None	N
E/W	0.9788	likely_pathogenic	0.9424	pathogenic	0.38	Stabilizing	0.992	D	0.612	neutral	None	None	None	None	N
E/Y	0.8939	likely_pathogenic	0.7668	pathogenic	0.375	Stabilizing	0.972	D	0.501	neutral	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.