TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7670	23233;23234;23235	chr2:178721011;178721010;178721009	chr2:179585738;179585737;179585736
N2AB	7353	22282;22283;22284	chr2:178721011;178721010;178721009	chr2:179585738;179585737;179585736
N2A	6426	19501;19502;19503	chr2:178721011;178721010;178721009	chr2:179585738;179585737;179585736
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-61
• Domain position: 63
• Structural Position: 143
• Q(SASA): 0.6301
• 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/K	None	None	0.425	N	0.226	0.104	0.134241683229	gnomAD-4.0.0	6.84451E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99789E-07	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	0.1421	likely_benign	0.1556	benign	-0.568	Destabilizing	0.139	N	0.186	neutral	N	0.413015057	None	None	N
E/C	0.7746	likely_pathogenic	0.8619	pathogenic	-0.015	Destabilizing	0.007	N	0.219	neutral	None	None	None	None	N
E/D	0.082	likely_benign	0.085	benign	-0.37	Destabilizing	0.001	N	0.112	neutral	N	0.38005449	None	None	N
E/F	0.669	likely_pathogenic	0.748	pathogenic	-0.363	Destabilizing	0.981	D	0.367	neutral	None	None	None	None	N
E/G	0.1129	likely_benign	0.1234	benign	-0.781	Destabilizing	0.001	N	0.114	neutral	N	0.402259346	None	None	N
E/H	0.2946	likely_benign	0.3631	ambiguous	-0.26	Destabilizing	0.944	D	0.208	neutral	None	None	None	None	N
E/I	0.443	ambiguous	0.5213	ambiguous	-0.029	Destabilizing	0.828	D	0.401	neutral	None	None	None	None	N
E/K	0.099	likely_benign	0.117	benign	0.392	Stabilizing	0.425	N	0.226	neutral	N	0.396370736	None	None	N
E/L	0.405	ambiguous	0.4683	ambiguous	-0.029	Destabilizing	0.704	D	0.379	neutral	None	None	None	None	N
E/M	0.4304	ambiguous	0.4968	ambiguous	0.222	Stabilizing	0.981	D	0.302	neutral	None	None	None	None	N
E/N	0.1481	likely_benign	0.175	benign	-0.075	Destabilizing	0.003	N	0.167	neutral	None	None	None	None	N
E/P	0.7508	likely_pathogenic	0.8266	pathogenic	-0.189	Destabilizing	0.828	D	0.363	neutral	None	None	None	None	N
E/Q	0.1121	likely_benign	0.1239	benign	-0.007	Destabilizing	0.784	D	0.271	neutral	N	0.400259191	None	None	N
E/R	0.1686	likely_benign	0.2043	benign	0.51	Stabilizing	0.704	D	0.217	neutral	None	None	None	None	N
E/S	0.1527	likely_benign	0.1763	benign	-0.209	Destabilizing	0.013	N	0.103	neutral	None	None	None	None	N
E/T	0.2063	likely_benign	0.2428	benign	-0.015	Destabilizing	0.329	N	0.278	neutral	None	None	None	None	N
E/V	0.2712	likely_benign	0.3168	benign	-0.189	Destabilizing	0.642	D	0.349	neutral	N	0.473140796	None	None	N
E/W	0.8184	likely_pathogenic	0.8797	pathogenic	-0.148	Destabilizing	0.995	D	0.314	neutral	None	None	None	None	N
E/Y	0.4693	ambiguous	0.5521	ambiguous	-0.1	Destabilizing	0.981	D	0.327	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.