TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27726	83401;83402;83403	chr2:178562956;178562955;178562954	chr2:179427683;179427682;179427681
N2AB	26085	78478;78479;78480	chr2:178562956;178562955;178562954	chr2:179427683;179427682;179427681
N2A	25158	75697;75698;75699	chr2:178562956;178562955;178562954	chr2:179427683;179427682;179427681
N2B	18661	56206;56207;56208	chr2:178562956;178562955;178562954	chr2:179427683;179427682;179427681
Novex-1	18786	56581;56582;56583	chr2:178562956;178562955;178562954	chr2:179427683;179427682;179427681
Novex-2	18853	56782;56783;56784	chr2:178562956;178562955;178562954	chr2:179427683;179427682;179427681
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-141
• Domain position: 51
• Structural Position: 131
• Q(SASA): 0.5514
• 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
S/G	None	None	0.003	N	0.197	0.067	None	gnomAD-4.0.0	8.89541E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.16936E-05	0	0
S/R	rs1704233145	None	0.015	N	0.259	0.143	0.183819452728	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
S/R	rs1704233145	None	0.015	N	0.259	0.143	0.183819452728	gnomAD-4.0.0	6.57436E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47063E-05	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
S/A	0.0902	likely_benign	0.1012	benign	-0.228	Destabilizing	0.373	N	0.352	neutral	None	None	None	None	N
S/C	0.207	likely_benign	0.2473	benign	-0.315	Destabilizing	0.994	D	0.355	neutral	N	0.469810351	None	None	N
S/D	0.3492	ambiguous	0.4074	ambiguous	0.275	Stabilizing	0.009	N	0.237	neutral	None	None	None	None	N
S/E	0.5022	ambiguous	0.5644	pathogenic	0.177	Stabilizing	0.59	D	0.275	neutral	None	None	None	None	N
S/F	0.4963	ambiguous	0.5941	pathogenic	-0.858	Destabilizing	0.984	D	0.396	neutral	None	None	None	None	N
S/G	0.0761	likely_benign	0.0817	benign	-0.319	Destabilizing	0.003	N	0.197	neutral	N	0.414876352	None	None	N
S/H	0.4216	ambiguous	0.4879	ambiguous	-0.781	Destabilizing	0.987	D	0.312	neutral	None	None	None	None	N
S/I	0.4333	ambiguous	0.5075	ambiguous	-0.123	Destabilizing	0.939	D	0.408	neutral	N	0.469556861	None	None	N
S/K	0.6584	likely_pathogenic	0.741	pathogenic	-0.392	Destabilizing	0.59	D	0.279	neutral	None	None	None	None	N
S/L	0.2156	likely_benign	0.2658	benign	-0.123	Destabilizing	0.742	D	0.4	neutral	None	None	None	None	N
S/M	0.3646	ambiguous	0.4151	ambiguous	-0.022	Destabilizing	0.996	D	0.327	neutral	None	None	None	None	N
S/N	0.1296	likely_benign	0.1627	benign	-0.148	Destabilizing	0.521	D	0.312	neutral	N	0.453880245	None	None	N
S/P	0.1013	likely_benign	0.1339	benign	-0.13	Destabilizing	0.953	D	0.324	neutral	None	None	None	None	N
S/Q	0.5129	ambiguous	0.5772	pathogenic	-0.371	Destabilizing	0.91	D	0.311	neutral	None	None	None	None	N
S/R	0.6146	likely_pathogenic	0.7136	pathogenic	-0.207	Destabilizing	0.015	N	0.259	neutral	N	0.456933108	None	None	N
S/T	0.1044	likely_benign	0.1218	benign	-0.258	Destabilizing	0.684	D	0.327	neutral	N	0.457186598	None	None	N
S/V	0.3511	ambiguous	0.4083	ambiguous	-0.13	Destabilizing	0.953	D	0.402	neutral	None	None	None	None	N
S/W	0.6321	likely_pathogenic	0.7026	pathogenic	-0.899	Destabilizing	0.996	D	0.519	neutral	None	None	None	None	N
S/Y	0.3992	ambiguous	0.4805	ambiguous	-0.597	Destabilizing	0.984	D	0.396	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.