TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24176	72751;72752;72753	chr2:178573606;178573605;178573604	chr2:179438333;179438332;179438331
N2AB	22535	67828;67829;67830	chr2:178573606;178573605;178573604	chr2:179438333;179438332;179438331
N2A	21608	65047;65048;65049	chr2:178573606;178573605;178573604	chr2:179438333;179438332;179438331
N2B	15111	45556;45557;45558	chr2:178573606;178573605;178573604	chr2:179438333;179438332;179438331
Novex-1	15236	45931;45932;45933	chr2:178573606;178573605;178573604	chr2:179438333;179438332;179438331
Novex-2	15303	46132;46133;46134	chr2:178573606;178573605;178573604	chr2:179438333;179438332;179438331
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: Fn3-63
• Domain position: 55
• Structural Position: 75
• Q(SASA): 0.5777
• 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/D	rs878854331	None	None	N	0.101	0.061	0.149567049428	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
E/Q	rs1553609326	None	0.117	N	0.432	0.163	0.323615622048	gnomAD-4.0.0	1.94898E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.37348E-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	0.1291	likely_benign	0.1347	benign	-0.446	Destabilizing	0.027	N	0.439	neutral	N	0.494911296	None	None	N
E/C	0.7391	likely_pathogenic	0.7897	pathogenic	-0.176	Destabilizing	0.935	D	0.491	neutral	None	None	None	None	N
E/D	0.0834	likely_benign	0.0932	benign	-0.327	Destabilizing	None	N	0.101	neutral	N	0.410639261	None	None	N
E/F	0.6828	likely_pathogenic	0.6931	pathogenic	-0.236	Destabilizing	0.791	D	0.433	neutral	None	None	None	None	N
E/G	0.1345	likely_benign	0.1428	benign	-0.667	Destabilizing	None	N	0.225	neutral	N	0.463569668	None	None	N
E/H	0.3579	ambiguous	0.3799	ambiguous	-0.04	Destabilizing	0.555	D	0.418	neutral	None	None	None	None	N
E/I	0.3646	ambiguous	0.3754	ambiguous	0.112	Stabilizing	0.555	D	0.438	neutral	None	None	None	None	N
E/K	0.1436	likely_benign	0.1478	benign	0.076	Stabilizing	0.117	N	0.415	neutral	N	0.470879643	None	None	N
E/L	0.3862	ambiguous	0.3956	ambiguous	0.112	Stabilizing	0.555	D	0.429	neutral	None	None	None	None	N
E/M	0.413	ambiguous	0.4292	ambiguous	0.184	Stabilizing	0.935	D	0.422	neutral	None	None	None	None	N
E/N	0.1486	likely_benign	0.1674	benign	-0.174	Destabilizing	0.081	N	0.385	neutral	None	None	None	None	N
E/P	0.6539	likely_pathogenic	0.6391	pathogenic	-0.054	Destabilizing	0.555	D	0.457	neutral	None	None	None	None	N
E/Q	0.1448	likely_benign	0.1481	benign	-0.129	Destabilizing	0.117	N	0.432	neutral	N	0.482310145	None	None	N
E/R	0.2548	likely_benign	0.2586	benign	0.357	Stabilizing	0.38	N	0.437	neutral	None	None	None	None	N
E/S	0.1533	likely_benign	0.1641	benign	-0.394	Destabilizing	0.081	N	0.401	neutral	None	None	None	None	N
E/T	0.1767	likely_benign	0.1907	benign	-0.219	Destabilizing	0.149	N	0.445	neutral	None	None	None	None	N
E/V	0.2123	likely_benign	0.2248	benign	-0.054	Destabilizing	0.484	N	0.423	neutral	N	0.480000558	None	None	N
E/W	0.8671	likely_pathogenic	0.8782	pathogenic	-0.067	Destabilizing	0.935	D	0.569	neutral	None	None	None	None	N
E/Y	0.5257	ambiguous	0.5655	pathogenic	0.001	Stabilizing	0.791	D	0.425	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.