TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6872	20839;20840;20841	chr2:178725590;178725589;178725588	chr2:179590317;179590316;179590315
N2AB	6555	19888;19889;19890	chr2:178725590;178725589;178725588	chr2:179590317;179590316;179590315
N2A	5628	17107;17108;17109	chr2:178725590;178725589;178725588	chr2:179590317;179590316;179590315
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-53
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.5811
• 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	rs376378443	0.114	0.134	N	0.288	0.194	None	gnomAD-2.1.1	1.8E-05	None	None	None	None	N	None	2.07142E-04	0	None	0	0	None	0	None	0	0	0
E/K	rs376378443	0.114	0.134	N	0.288	0.194	None	gnomAD-3.1.2	5.92E-05	None	None	None	None	N	None	2.17192E-04	0	0	0	0	None	0	0	0	0	0
E/K	rs376378443	0.114	0.134	N	0.288	0.194	None	gnomAD-4.0.0	8.06738E-06	None	None	None	None	N	None	1.60466E-04	0	None	0	0	None	0	0	0	0	1.60395E-05

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	0.1354	likely_benign	0.1129	benign	-0.728	Destabilizing	0.704	D	0.485	neutral	N	0.460691574	None	None	N
E/C	0.8033	likely_pathogenic	0.7434	pathogenic	-0.405	Destabilizing	0.999	D	0.559	neutral	None	None	None	None	N
E/D	0.3177	likely_benign	0.2272	benign	-0.957	Destabilizing	0.92	D	0.581	neutral	N	0.499729965	None	None	N
E/F	0.6111	likely_pathogenic	0.5175	ambiguous	-0.206	Destabilizing	0.991	D	0.591	neutral	None	None	None	None	N
E/G	0.23	likely_benign	0.1835	benign	-1.063	Destabilizing	0.92	D	0.574	neutral	N	0.469036656	None	None	N
E/H	0.42	ambiguous	0.3282	benign	-0.353	Destabilizing	0.997	D	0.564	neutral	None	None	None	None	N
E/I	0.2214	likely_benign	0.1794	benign	0.172	Stabilizing	0.17	N	0.463	neutral	None	None	None	None	N
E/K	0.1166	likely_benign	0.1045	benign	-0.356	Destabilizing	0.134	N	0.288	neutral	N	0.450127864	None	None	N
E/L	0.293	likely_benign	0.2376	benign	0.172	Stabilizing	0.759	D	0.529	neutral	None	None	None	None	N
E/M	0.3192	likely_benign	0.2674	benign	0.462	Stabilizing	0.991	D	0.562	neutral	None	None	None	None	N
E/N	0.3476	ambiguous	0.2549	benign	-0.861	Destabilizing	0.939	D	0.539	neutral	None	None	None	None	N
E/P	0.9195	likely_pathogenic	0.9005	pathogenic	-0.107	Destabilizing	0.991	D	0.606	neutral	None	None	None	None	N
E/Q	0.1048	likely_benign	0.0905	benign	-0.745	Destabilizing	0.92	D	0.527	neutral	N	0.421095823	None	None	N
E/R	0.2072	likely_benign	0.1799	benign	-0.058	Destabilizing	0.884	D	0.542	neutral	None	None	None	None	N
E/S	0.2025	likely_benign	0.1542	benign	-1.108	Destabilizing	0.373	N	0.278	neutral	None	None	None	None	N
E/T	0.1575	likely_benign	0.1307	benign	-0.83	Destabilizing	0.884	D	0.601	neutral	None	None	None	None	N
E/V	0.1262	likely_benign	0.1094	benign	-0.107	Destabilizing	0.134	N	0.392	neutral	N	0.445855407	None	None	N
E/W	0.8619	likely_pathogenic	0.8105	pathogenic	0.053	Stabilizing	0.999	D	0.601	neutral	None	None	None	None	N
E/Y	0.5536	ambiguous	0.4655	ambiguous	0.052	Stabilizing	0.997	D	0.577	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.