TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32351	97276;97277;97278	chr2:178542803;178542802;178542801	chr2:179407530;179407529;179407528
N2AB	30710	92353;92354;92355	chr2:178542803;178542802;178542801	chr2:179407530;179407529;179407528
N2A	29783	89572;89573;89574	chr2:178542803;178542802;178542801	chr2:179407530;179407529;179407528
N2B	23286	70081;70082;70083	chr2:178542803;178542802;178542801	chr2:179407530;179407529;179407528
Novex-1	23411	70456;70457;70458	chr2:178542803;178542802;178542801	chr2:179407530;179407529;179407528
Novex-2	23478	70657;70658;70659	chr2:178542803;178542802;178542801	chr2:179407530;179407529;179407528
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-154
• Domain position: 45
• Structural Position: 102
• Q(SASA): 0.9979
• 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/G	rs879109633	None	0.722	N	0.438	0.228	0.230578612272	gnomAD-4.0.0	3.18245E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71661E-06	0	0
E/K	rs727504879	0.789	0.722	N	0.4	0.19	0.17948927462	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.68E-05	0
E/K	rs727504879	0.789	0.722	N	0.4	0.19	0.17948927462	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
E/K	rs727504879	0.789	0.722	N	0.4	0.19	0.17948927462	gnomAD-4.0.0	8.05613E-06	None	None	None	None	N	None	1.33518E-05	0	None	0	0	None	0	0	9.32382E-06	0	1.60102E-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	0.188	likely_benign	0.2007	benign	0.047	Stabilizing	0.722	D	0.423	neutral	N	0.477199822	None	None	N
E/C	0.8768	likely_pathogenic	0.8889	pathogenic	-0.213	Destabilizing	0.996	D	0.592	neutral	None	None	None	None	N
E/D	0.0889	likely_benign	0.0914	benign	-0.419	Destabilizing	0.001	N	0.229	neutral	N	0.406857089	None	None	N
E/F	0.8414	likely_pathogenic	0.8474	pathogenic	-0.037	Destabilizing	0.987	D	0.532	neutral	None	None	None	None	N
E/G	0.1517	likely_benign	0.168	benign	-0.039	Destabilizing	0.722	D	0.438	neutral	N	0.441623024	None	None	N
E/H	0.4992	ambiguous	0.5169	ambiguous	0.581	Stabilizing	0.987	D	0.417	neutral	None	None	None	None	N
E/I	0.5184	ambiguous	0.5281	ambiguous	0.213	Stabilizing	0.961	D	0.53	neutral	None	None	None	None	N
E/K	0.2126	likely_benign	0.2359	benign	0.403	Stabilizing	0.722	D	0.4	neutral	N	0.462750444	None	None	N
E/L	0.5023	ambiguous	0.5132	ambiguous	0.213	Stabilizing	0.961	D	0.528	neutral	None	None	None	None	N
E/M	0.6011	likely_pathogenic	0.6101	pathogenic	-0.02	Destabilizing	0.996	D	0.507	neutral	None	None	None	None	N
E/N	0.239	likely_benign	0.2579	benign	0.159	Stabilizing	0.633	D	0.401	neutral	None	None	None	None	N
E/P	0.3105	likely_benign	0.3395	benign	0.174	Stabilizing	0.961	D	0.415	neutral	None	None	None	None	N
E/Q	0.1781	likely_benign	0.189	benign	0.165	Stabilizing	0.722	D	0.369	neutral	N	0.470716566	None	None	N
E/R	0.3359	likely_benign	0.3703	ambiguous	0.582	Stabilizing	0.961	D	0.42	neutral	None	None	None	None	N
E/S	0.1796	likely_benign	0.1933	benign	0.05	Stabilizing	0.633	D	0.403	neutral	None	None	None	None	N
E/T	0.2629	likely_benign	0.2778	benign	0.134	Stabilizing	0.775	D	0.389	neutral	None	None	None	None	N
E/V	0.3337	likely_benign	0.3424	ambiguous	0.174	Stabilizing	0.949	D	0.457	neutral	N	0.45664362	None	None	N
E/W	0.9152	likely_pathogenic	0.9177	pathogenic	-0.026	Destabilizing	0.996	D	0.616	neutral	None	None	None	None	N
E/Y	0.7087	likely_pathogenic	0.7201	pathogenic	0.172	Stabilizing	0.987	D	0.483	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.