TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31396	94411;94412;94413	chr2:178547440;178547439;178547438	chr2:179412167;179412166;179412165
N2AB	29755	89488;89489;89490	chr2:178547440;178547439;178547438	chr2:179412167;179412166;179412165
N2A	28828	86707;86708;86709	chr2:178547440;178547439;178547438	chr2:179412167;179412166;179412165
N2B	22331	67216;67217;67218	chr2:178547440;178547439;178547438	chr2:179412167;179412166;179412165
Novex-1	22456	67591;67592;67593	chr2:178547440;178547439;178547438	chr2:179412167;179412166;179412165
Novex-2	22523	67792;67793;67794	chr2:178547440;178547439;178547438	chr2:179412167;179412166;179412165
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: Fn3-116
• Domain position: 89
• Structural Position: 122
• Q(SASA): 0.5508
• 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/A	rs768420352	-0.569	0.997	N	0.791	0.326	0.528308644755	gnomAD-2.1.1	1.1E-05	None	None	None	None	N	None	0	8.67E-05	None	0	0	None	0	None	0	0	0
E/A	rs768420352	-0.569	0.997	N	0.791	0.326	0.528308644755	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
E/A	rs768420352	-0.569	0.997	N	0.791	0.326	0.528308644755	gnomAD-4.0.0	5.15432E-06	None	None	None	None	N	None	0	6.8334E-05	None	0	0	None	0	0	0	0	0
E/G	None	None	0.999	N	0.734	0.351	0.604527667468	gnomAD-4.0.0	1.603E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.88281E-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	0.21	likely_benign	0.235	benign	-0.952	Destabilizing	0.997	D	0.791	deleterious	N	0.495594447	None	None	N
E/C	0.8176	likely_pathogenic	0.842	pathogenic	-0.425	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
E/D	0.1714	likely_benign	0.1646	benign	-0.795	Destabilizing	0.997	D	0.762	deleterious	N	0.491516779	None	None	N
E/F	0.7296	likely_pathogenic	0.7819	pathogenic	-0.181	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
E/G	0.354	ambiguous	0.3939	ambiguous	-1.306	Destabilizing	0.999	D	0.734	deleterious	N	0.520762251	None	None	N
E/H	0.5963	likely_pathogenic	0.6158	pathogenic	-0.209	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
E/I	0.2642	likely_benign	0.3227	benign	0.015	Stabilizing	0.999	D	0.838	deleterious	None	None	None	None	N
E/K	0.3443	ambiguous	0.3866	ambiguous	-0.176	Destabilizing	0.997	D	0.815	deleterious	N	0.515796361	None	None	N
E/L	0.2976	likely_benign	0.3629	ambiguous	0.015	Stabilizing	0.999	D	0.755	deleterious	None	None	None	None	N
E/M	0.4361	ambiguous	0.4965	ambiguous	0.368	Stabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
E/N	0.3821	ambiguous	0.41	ambiguous	-0.859	Destabilizing	0.999	D	0.787	deleterious	None	None	None	None	N
E/P	0.5342	ambiguous	0.519	ambiguous	-0.287	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
E/Q	0.2019	likely_benign	0.2134	benign	-0.731	Destabilizing	0.999	D	0.803	deleterious	N	0.480491709	None	None	N
E/R	0.4835	ambiguous	0.5201	ambiguous	0.162	Stabilizing	0.999	D	0.783	deleterious	None	None	None	None	N
E/S	0.3045	likely_benign	0.3303	benign	-1.138	Destabilizing	0.998	D	0.809	deleterious	None	None	None	None	N
E/T	0.2567	likely_benign	0.2915	benign	-0.823	Destabilizing	0.999	D	0.744	deleterious	None	None	None	None	N
E/V	0.1531	likely_benign	0.1832	benign	-0.287	Destabilizing	0.999	D	0.774	deleterious	N	0.49563452	None	None	N
E/W	0.9241	likely_pathogenic	0.9372	pathogenic	0.229	Stabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
E/Y	0.6648	likely_pathogenic	0.7057	pathogenic	0.141	Stabilizing	1.0	D	0.859	deleterious	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.