TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6899	20920;20921;20922	chr2:178725509;178725508;178725507	chr2:179590236;179590235;179590234
N2AB	6582	19969;19970;19971	chr2:178725509;178725508;178725507	chr2:179590236;179590235;179590234
N2A	5655	17188;17189;17190	chr2:178725509;178725508;178725507	chr2:179590236;179590235;179590234
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-53
• Domain position: 46
• Structural Position: 111
• Q(SASA): 0.8179
• 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/G	rs777803266	-0.193	0.989	N	0.391	0.338	0.288727942641	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/G	rs777803266	-0.193	0.989	N	0.391	0.338	0.288727942641	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/G	rs777803266	-0.193	0.989	N	0.391	0.338	0.288727942641	gnomAD-4.0.0	3.8452E-06	None	None	None	None	N	None	3.38409E-05	0	None	0	0	None	0	0	0	1.34109E-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	0.1988	likely_benign	0.1936	benign	0.03	Stabilizing	0.994	D	0.427	neutral	N	0.461452559	None	None	N
E/C	0.8975	likely_pathogenic	0.9095	pathogenic	-0.187	Destabilizing	1.0	D	0.599	neutral	None	None	None	None	N
E/D	0.0988	likely_benign	0.0874	benign	-0.44	Destabilizing	0.217	N	0.272	neutral	N	0.415745931	None	None	N
E/F	0.8374	likely_pathogenic	0.8642	pathogenic	-0.106	Destabilizing	1.0	D	0.527	neutral	None	None	None	None	N
E/G	0.1378	likely_benign	0.1353	benign	-0.041	Destabilizing	0.989	D	0.391	neutral	N	0.499804535	None	None	N
E/H	0.5235	ambiguous	0.5538	ambiguous	0.473	Stabilizing	0.999	D	0.445	neutral	None	None	None	None	N
E/I	0.586	likely_pathogenic	0.58	pathogenic	0.156	Stabilizing	1.0	D	0.54	neutral	None	None	None	None	N
E/K	0.1339	likely_benign	0.157	benign	0.341	Stabilizing	0.989	D	0.448	neutral	N	0.485915305	None	None	N
E/L	0.5647	likely_pathogenic	0.5791	pathogenic	0.156	Stabilizing	0.999	D	0.531	neutral	None	None	None	None	N
E/M	0.6514	likely_pathogenic	0.6657	pathogenic	-0.028	Destabilizing	1.0	D	0.493	neutral	None	None	None	None	N
E/N	0.2539	likely_benign	0.2371	benign	0.188	Stabilizing	0.784	D	0.306	neutral	None	None	None	None	N
E/P	0.3454	ambiguous	0.3382	benign	0.129	Stabilizing	1.0	D	0.421	neutral	None	None	None	None	N
E/Q	0.1885	likely_benign	0.1972	benign	0.181	Stabilizing	0.998	D	0.423	neutral	N	0.457440087	None	None	N
E/R	0.2428	likely_benign	0.2922	benign	0.48	Stabilizing	0.999	D	0.439	neutral	None	None	None	None	N
E/S	0.2132	likely_benign	0.2046	benign	0.064	Stabilizing	0.992	D	0.419	neutral	None	None	None	None	N
E/T	0.3224	likely_benign	0.31	benign	0.134	Stabilizing	0.992	D	0.385	neutral	None	None	None	None	N
E/V	0.3727	ambiguous	0.3726	ambiguous	0.129	Stabilizing	0.999	D	0.458	neutral	N	0.481331241	None	None	N
E/W	0.8832	likely_pathogenic	0.9157	pathogenic	-0.115	Destabilizing	1.0	D	0.615	neutral	None	None	None	None	N
E/Y	0.6958	likely_pathogenic	0.7271	pathogenic	0.094	Stabilizing	1.0	D	0.471	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.