TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29206	87841;87842;87843	chr2:178557738;178557737;178557736	chr2:179422465;179422464;179422463
N2AB	27565	82918;82919;82920	chr2:178557738;178557737;178557736	chr2:179422465;179422464;179422463
N2A	26638	80137;80138;80139	chr2:178557738;178557737;178557736	chr2:179422465;179422464;179422463
N2B	20141	60646;60647;60648	chr2:178557738;178557737;178557736	chr2:179422465;179422464;179422463
Novex-1	20266	61021;61022;61023	chr2:178557738;178557737;178557736	chr2:179422465;179422464;179422463
Novex-2	20333	61222;61223;61224	chr2:178557738;178557737;178557736	chr2:179422465;179422464;179422463
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: Fn3-100
• Domain position: 70
• Structural Position: 102
• Q(SASA): 0.2927
• 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/A	None	None	0.285	N	0.369	0.173	0.223847106136	gnomAD-4.0.0	6.84166E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	1.65645E-05
E/G	rs1702073480	None	0.491	N	0.391	0.218	0.270001397563	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/G	rs1702073480	None	0.491	N	0.391	0.218	0.270001397563	gnomAD-4.0.0	1.23925E-06	None	None	None	None	I	None	0	0	None	3.37815E-05	0	None	0	0	8.47554E-07	0	0
E/K	rs1364550008	None	0.491	N	0.29	0.223	0.219573609325	gnomAD-4.0.0	1.59104E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85778E-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	0.1758	likely_benign	0.1817	benign	-0.896	Destabilizing	0.285	N	0.369	neutral	N	0.398152753	None	None	I
E/C	0.7413	likely_pathogenic	0.7408	pathogenic	-0.402	Destabilizing	0.991	D	0.429	neutral	None	None	None	None	I
E/D	0.2145	likely_benign	0.2296	benign	-1.033	Destabilizing	0.003	N	0.109	neutral	N	0.481867428	None	None	I
E/F	0.7391	likely_pathogenic	0.726	pathogenic	-0.405	Destabilizing	0.004	N	0.278	neutral	None	None	None	None	I
E/G	0.2543	likely_benign	0.2458	benign	-1.245	Destabilizing	0.491	N	0.391	neutral	N	0.420261608	None	None	I
E/H	0.4879	ambiguous	0.5062	ambiguous	-0.625	Destabilizing	0.965	D	0.369	neutral	None	None	None	None	I
E/I	0.3067	likely_benign	0.3332	benign	0.049	Stabilizing	0.39	N	0.386	neutral	None	None	None	None	I
E/K	0.1389	likely_benign	0.1635	benign	-0.484	Destabilizing	0.491	N	0.29	neutral	N	0.406849594	None	None	I
E/L	0.3864	ambiguous	0.3844	ambiguous	0.049	Stabilizing	0.002	N	0.182	neutral	None	None	None	None	I
E/M	0.3674	ambiguous	0.3779	ambiguous	0.502	Stabilizing	0.818	D	0.418	neutral	None	None	None	None	I
E/N	0.2896	likely_benign	0.3128	benign	-0.955	Destabilizing	0.39	N	0.397	neutral	None	None	None	None	I
E/P	0.9635	likely_pathogenic	0.9651	pathogenic	-0.245	Destabilizing	0.901	D	0.445	neutral	None	None	None	None	I
E/Q	0.131	likely_benign	0.1358	benign	-0.838	Destabilizing	0.662	D	0.409	neutral	N	0.42595543	None	None	I
E/R	0.2617	likely_benign	0.2661	benign	-0.211	Destabilizing	0.901	D	0.394	neutral	None	None	None	None	I
E/S	0.2261	likely_benign	0.2411	benign	-1.247	Destabilizing	0.561	D	0.249	neutral	None	None	None	None	I
E/T	0.2182	likely_benign	0.2364	benign	-0.957	Destabilizing	0.561	D	0.365	neutral	None	None	None	None	I
E/V	0.1822	likely_benign	0.1944	benign	-0.245	Destabilizing	0.013	N	0.269	neutral	N	0.393728368	None	None	I
E/W	0.9151	likely_pathogenic	0.9032	pathogenic	-0.138	Destabilizing	0.991	D	0.437	neutral	None	None	None	None	I
E/Y	0.6463	likely_pathogenic	0.6372	pathogenic	-0.144	Destabilizing	0.692	D	0.453	neutral	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.