TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31458	94597;94598;94599	chr2:178547153;178547152;178547151	chr2:179411880;179411879;179411878
N2AB	29817	89674;89675;89676	chr2:178547153;178547152;178547151	chr2:179411880;179411879;179411878
N2A	28890	86893;86894;86895	chr2:178547153;178547152;178547151	chr2:179411880;179411879;179411878
N2B	22393	67402;67403;67404	chr2:178547153;178547152;178547151	chr2:179411880;179411879;179411878
Novex-1	22518	67777;67778;67779	chr2:178547153;178547152;178547151	chr2:179411880;179411879;179411878
Novex-2	22585	67978;67979;67980	chr2:178547153;178547152;178547151	chr2:179411880;179411879;179411878
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: Fn3-117
• Domain position: 51
• Structural Position: 68
• Q(SASA): 0.203
• 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
E/G	rs763832963	-1.331	0.993	N	0.714	0.492	0.369309618794	gnomAD-2.1.1	8.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.77E-05	0
E/G	rs763832963	-1.331	0.993	N	0.714	0.492	0.369309618794	gnomAD-4.0.0	3.18238E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.71644E-06	0	0
E/K	rs1697558384	None	0.977	N	0.497	0.384	0.326616659874	gnomAD-4.0.0	1.5912E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85827E-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	0.245	likely_benign	0.2518	benign	-0.4	Destabilizing	0.977	D	0.596	neutral	N	0.353863258	None	None	I
E/C	0.8583	likely_pathogenic	0.8691	pathogenic	-0.186	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
E/D	0.2895	likely_benign	0.2042	benign	-1.279	Destabilizing	0.117	N	0.269	neutral	N	0.486811887	None	None	I
E/F	0.9428	likely_pathogenic	0.9444	pathogenic	0.359	Stabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
E/G	0.4362	ambiguous	0.4188	ambiguous	-0.857	Destabilizing	0.993	D	0.714	prob.delet.	N	0.440924882	None	None	I
E/H	0.8524	likely_pathogenic	0.8299	pathogenic	-0.006	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
E/I	0.5689	likely_pathogenic	0.5778	pathogenic	0.87	Stabilizing	0.998	D	0.825	deleterious	None	None	None	None	I
E/K	0.6826	likely_pathogenic	0.655	pathogenic	-0.48	Destabilizing	0.977	D	0.497	neutral	N	0.474901383	None	None	I
E/L	0.7177	likely_pathogenic	0.7254	pathogenic	0.87	Stabilizing	0.998	D	0.798	deleterious	None	None	None	None	I
E/M	0.7219	likely_pathogenic	0.743	pathogenic	1.326	Stabilizing	1.0	D	0.81	deleterious	None	None	None	None	I
E/N	0.6332	likely_pathogenic	0.5701	pathogenic	-1.158	Destabilizing	0.99	D	0.697	prob.neutral	None	None	None	None	I
E/P	0.9773	likely_pathogenic	0.9641	pathogenic	0.47	Stabilizing	0.998	D	0.81	deleterious	None	None	None	None	I
E/Q	0.349	ambiguous	0.3562	ambiguous	-0.873	Destabilizing	0.997	D	0.643	neutral	N	0.474034591	None	None	I
E/R	0.8081	likely_pathogenic	0.7987	pathogenic	-0.302	Destabilizing	0.998	D	0.733	prob.delet.	None	None	None	None	I
E/S	0.4715	ambiguous	0.4479	ambiguous	-1.51	Destabilizing	0.983	D	0.547	neutral	None	None	None	None	I
E/T	0.5096	ambiguous	0.5131	ambiguous	-1.107	Destabilizing	0.998	D	0.749	deleterious	None	None	None	None	I
E/V	0.2972	likely_benign	0.3196	benign	0.47	Stabilizing	0.997	D	0.785	deleterious	N	0.327850093	None	None	I
E/W	0.9833	likely_pathogenic	0.9829	pathogenic	0.51	Stabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
E/Y	0.876	likely_pathogenic	0.8636	pathogenic	0.619	Stabilizing	1.0	D	0.813	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.