TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32065	96418;96419;96420	chr2:178543951;178543950;178543949	chr2:179408678;179408677;179408676
N2AB	30424	91495;91496;91497	chr2:178543951;178543950;178543949	chr2:179408678;179408677;179408676
N2A	29497	88714;88715;88716	chr2:178543951;178543950;178543949	chr2:179408678;179408677;179408676
N2B	23000	69223;69224;69225	chr2:178543951;178543950;178543949	chr2:179408678;179408677;179408676
Novex-1	23125	69598;69599;69600	chr2:178543951;178543950;178543949	chr2:179408678;179408677;179408676
Novex-2	23192	69799;69800;69801	chr2:178543951;178543950;178543949	chr2:179408678;179408677;179408676
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-153
• Domain position: 49
• Structural Position: 131
• Q(SASA): 0.6125
• 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	None	None	None	N	0.126	0.063	0.0954503805726	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	2.75482E-04	None	0	0	0	0	0
E/K	rs1695839885	None	0.117	N	0.363	0.134	0.180583059064	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs1695839885	None	0.117	N	0.363	0.134	0.180583059064	gnomAD-4.0.0	6.57479E-06	None	None	None	None	N	None	2.41441E-05	0	None	0	0	None	0	0	0	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	0.1403	likely_benign	0.1331	benign	-0.017	Destabilizing	0.117	N	0.381	neutral	N	0.507733372	None	None	N
E/C	0.8129	likely_pathogenic	0.7775	pathogenic	-0.033	Destabilizing	0.935	D	0.481	neutral	None	None	None	None	N
E/D	0.063	likely_benign	0.0596	benign	-0.252	Destabilizing	None	N	0.126	neutral	N	0.403374067	None	None	N
E/F	0.797	likely_pathogenic	0.7353	pathogenic	-0.034	Destabilizing	0.791	D	0.43	neutral	None	None	None	None	N
E/G	0.1402	likely_benign	0.1225	benign	-0.144	Destabilizing	0.062	N	0.399	neutral	N	0.444505826	None	None	N
E/H	0.4637	ambiguous	0.4156	ambiguous	0.459	Stabilizing	0.555	D	0.297	neutral	None	None	None	None	N
E/I	0.4579	ambiguous	0.4033	ambiguous	0.259	Stabilizing	0.555	D	0.435	neutral	None	None	None	None	N
E/K	0.2097	likely_benign	0.1748	benign	0.544	Stabilizing	0.117	N	0.363	neutral	N	0.463654521	None	None	N
E/L	0.4786	ambiguous	0.4194	ambiguous	0.259	Stabilizing	0.38	N	0.43	neutral	None	None	None	None	N
E/M	0.5517	ambiguous	0.5	ambiguous	0.125	Stabilizing	0.935	D	0.422	neutral	None	None	None	None	N
E/N	0.1756	likely_benign	0.1505	benign	0.248	Stabilizing	0.001	N	0.187	neutral	None	None	None	None	N
E/P	0.2969	likely_benign	0.2673	benign	0.186	Stabilizing	0.555	D	0.357	neutral	None	None	None	None	N
E/Q	0.1848	likely_benign	0.1729	benign	0.276	Stabilizing	0.117	N	0.351	neutral	N	0.508080089	None	None	N
E/R	0.3303	likely_benign	0.2817	benign	0.706	Stabilizing	0.38	N	0.309	neutral	None	None	None	None	N
E/S	0.1323	likely_benign	0.123	benign	0.134	Stabilizing	0.081	N	0.337	neutral	None	None	None	None	N
E/T	0.2163	likely_benign	0.2003	benign	0.249	Stabilizing	0.149	N	0.395	neutral	None	None	None	None	N
E/V	0.2761	likely_benign	0.2448	benign	0.186	Stabilizing	0.484	N	0.407	neutral	N	0.456136641	None	None	N
E/W	0.9093	likely_pathogenic	0.8662	pathogenic	0.02	Stabilizing	0.935	D	0.562	neutral	None	None	None	None	N
E/Y	0.6061	likely_pathogenic	0.5359	ambiguous	0.193	Stabilizing	0.791	D	0.407	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.