TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4726	14401;14402;14403	chr2:178738277;178738276;178738275	chr2:179603004;179603003;179603002
N2AB	4409	13450;13451;13452	chr2:178738277;178738276;178738275	chr2:179603004;179603003;179603002
N2A	3482	10669;10670;10671	chr2:178738277;178738276;178738275	chr2:179603004;179603003;179603002
N2B	4363	13312;13313;13314	chr2:178738277;178738276;178738275	chr2:179603004;179603003;179603002
Novex-1	4488	13687;13688;13689	chr2:178738277;178738276;178738275	chr2:179603004;179603003;179603002
Novex-2	4555	13888;13889;13890	chr2:178738277;178738276;178738275	chr2:179603004;179603003;179603002
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-30
• Domain position: 27
• Structural Position: 41
• Q(SASA): 0.5624
• 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
A/V	rs1241571397	0.084	0.031	N	0.278	0.188	0.541602255418	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
A/V	rs1241571397	0.084	0.031	N	0.278	0.188	0.541602255418	gnomAD-4.0.0	1.59192E-06	None	None	None	None	I	None	0	2.28718E-05	None	0	0	None	0	0	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
A/C	0.6037	likely_pathogenic	0.6412	pathogenic	-0.651	Destabilizing	0.973	D	0.53	neutral	None	None	None	None	I
A/D	0.6538	likely_pathogenic	0.7994	pathogenic	-1.279	Destabilizing	0.782	D	0.683	prob.neutral	N	0.484833154	None	None	I
A/E	0.5327	ambiguous	0.698	pathogenic	-1.301	Destabilizing	0.704	D	0.497	neutral	None	None	None	None	I
A/F	0.4398	ambiguous	0.5611	ambiguous	-0.914	Destabilizing	0.906	D	0.717	prob.delet.	None	None	None	None	I
A/G	0.2849	likely_benign	0.3692	ambiguous	-1.06	Destabilizing	0.338	N	0.493	neutral	N	0.487136109	None	None	I
A/H	0.6975	likely_pathogenic	0.7862	pathogenic	-1.299	Destabilizing	0.973	D	0.718	prob.delet.	None	None	None	None	I
A/I	0.2783	likely_benign	0.3931	ambiguous	-0.29	Destabilizing	0.404	N	0.517	neutral	None	None	None	None	I
A/K	0.7368	likely_pathogenic	0.8504	pathogenic	-1.243	Destabilizing	0.704	D	0.506	neutral	None	None	None	None	I
A/L	0.2456	likely_benign	0.3577	ambiguous	-0.29	Destabilizing	0.404	N	0.526	neutral	None	None	None	None	I
A/M	0.3235	likely_benign	0.4483	ambiguous	-0.239	Destabilizing	0.973	D	0.571	neutral	None	None	None	None	I
A/N	0.5461	ambiguous	0.6833	pathogenic	-0.937	Destabilizing	0.704	D	0.698	prob.neutral	None	None	None	None	I
A/P	0.5668	likely_pathogenic	0.7346	pathogenic	-0.424	Destabilizing	0.879	D	0.549	neutral	N	0.487569141	None	None	I
A/Q	0.579	likely_pathogenic	0.7056	pathogenic	-1.081	Destabilizing	0.826	D	0.552	neutral	None	None	None	None	I
A/R	0.6389	likely_pathogenic	0.763	pathogenic	-0.886	Destabilizing	0.826	D	0.545	neutral	None	None	None	None	I
A/S	0.1312	likely_benign	0.1508	benign	-1.195	Destabilizing	0.007	N	0.29	neutral	N	0.484833154	None	None	I
A/T	0.1304	likely_benign	0.1779	benign	-1.131	Destabilizing	0.013	N	0.297	neutral	N	0.484543749	None	None	I
A/V	0.1335	likely_benign	0.188	benign	-0.424	Destabilizing	0.031	N	0.278	neutral	N	0.465506486	None	None	I
A/W	0.8915	likely_pathogenic	0.9387	pathogenic	-1.312	Destabilizing	0.991	D	0.749	deleterious	None	None	None	None	I
A/Y	0.6661	likely_pathogenic	0.7683	pathogenic	-0.89	Destabilizing	0.906	D	0.71	prob.delet.	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.