TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32827	98704;98705;98706	chr2:178539586;178539585;178539584	chr2:179404313;179404312;179404311
N2AB	31186	93781;93782;93783	chr2:178539586;178539585;178539584	chr2:179404313;179404312;179404311
N2A	30259	91000;91001;91002	chr2:178539586;178539585;178539584	chr2:179404313;179404312;179404311
N2B	23762	71509;71510;71511	chr2:178539586;178539585;178539584	chr2:179404313;179404312;179404311
Novex-1	23887	71884;71885;71886	chr2:178539586;178539585;178539584	chr2:179404313;179404312;179404311
Novex-2	23954	72085;72086;72087	chr2:178539586;178539585;178539584	chr2:179404313;179404312;179404311
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-127
• Domain position: 33
• Structural Position: 34
• Q(SASA): 0.9513
• 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
D/G	rs780460404	-0.199	1.0	N	0.665	0.463	0.201204373187	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	5.79E-05	None	0	0	None	0	None	0	8.89E-06	0
D/G	rs780460404	-0.199	1.0	N	0.665	0.463	0.201204373187	gnomAD-4.0.0	4.77327E-06	None	None	None	None	N	None	0	4.57268E-05	None	0	0	None	0	0	2.85802E-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
D/A	0.1518	likely_benign	0.1721	benign	-0.171	Destabilizing	1.0	D	0.704	prob.neutral	N	0.390407556	None	None	N
D/C	0.6778	likely_pathogenic	0.6909	pathogenic	0.039	Stabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
D/E	0.1322	likely_benign	0.1377	benign	-0.256	Destabilizing	1.0	D	0.402	neutral	N	0.34728871	None	None	N
D/F	0.6792	likely_pathogenic	0.7183	pathogenic	-0.131	Destabilizing	1.0	D	0.611	neutral	None	None	None	None	N
D/G	0.1912	likely_benign	0.215	benign	-0.366	Destabilizing	1.0	D	0.665	neutral	N	0.436198561	None	None	N
D/H	0.3203	likely_benign	0.3569	ambiguous	0.048	Stabilizing	1.0	D	0.593	neutral	N	0.486723382	None	None	N
D/I	0.4302	ambiguous	0.4701	ambiguous	0.292	Stabilizing	1.0	D	0.641	neutral	None	None	None	None	N
D/K	0.3227	likely_benign	0.3657	ambiguous	0.301	Stabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	N
D/L	0.4212	ambiguous	0.4561	ambiguous	0.292	Stabilizing	1.0	D	0.661	neutral	None	None	None	None	N
D/M	0.6256	likely_pathogenic	0.6569	pathogenic	0.353	Stabilizing	1.0	D	0.663	neutral	None	None	None	None	N
D/N	0.1146	likely_benign	0.1204	benign	0.069	Stabilizing	1.0	D	0.641	neutral	N	0.464499883	None	None	N
D/P	0.3989	ambiguous	0.4439	ambiguous	0.16	Stabilizing	1.0	D	0.671	neutral	None	None	None	None	N
D/Q	0.3005	likely_benign	0.3297	benign	0.1	Stabilizing	1.0	D	0.657	neutral	None	None	None	None	N
D/R	0.3687	ambiguous	0.4215	ambiguous	0.481	Stabilizing	1.0	D	0.67	neutral	None	None	None	None	N
D/S	0.1354	likely_benign	0.1466	benign	-0.059	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	N
D/T	0.2711	likely_benign	0.3	benign	0.09	Stabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
D/V	0.2371	likely_benign	0.263	benign	0.16	Stabilizing	1.0	D	0.662	neutral	N	0.471273927	None	None	N
D/W	0.9043	likely_pathogenic	0.9187	pathogenic	-0.028	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
D/Y	0.3102	likely_benign	0.3324	benign	0.102	Stabilizing	1.0	D	0.597	neutral	N	0.487070099	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.