TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6556	19891;19892;19893	chr2:178728158;178728157;178728156	chr2:179592885;179592884;179592883
N2AB	6239	18940;18941;18942	chr2:178728158;178728157;178728156	chr2:179592885;179592884;179592883
N2A	5312	16159;16160;16161	chr2:178728158;178728157;178728156	chr2:179592885;179592884;179592883
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: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-49
• Domain position: 76
• Structural Position: 159
• Q(SASA): 0.2703
• 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
S/L	rs2154306280	None	0.042	N	0.511	0.201	0.621426341079	gnomAD-4.0.0	2.33534E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.06722E-05	0	0
S/P	None	None	0.301	N	0.431	0.335	0.379881503574	gnomAD-4.0.0	1.6052E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.45012E-05	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
S/A	0.0832	likely_benign	0.0785	benign	-0.595	Destabilizing	None	N	0.101	neutral	N	0.453097251	None	None	N
S/C	0.1202	likely_benign	0.1175	benign	-0.661	Destabilizing	0.667	D	0.468	neutral	None	None	None	None	N
S/D	0.4303	ambiguous	0.4257	ambiguous	-1.131	Destabilizing	0.055	N	0.329	neutral	None	None	None	None	N
S/E	0.4368	ambiguous	0.4297	ambiguous	-1.145	Destabilizing	0.002	N	0.125	neutral	None	None	None	None	N
S/F	0.1796	likely_benign	0.1534	benign	-0.979	Destabilizing	0.497	N	0.516	neutral	None	None	None	None	N
S/G	0.1145	likely_benign	0.1174	benign	-0.803	Destabilizing	0.055	N	0.36	neutral	None	None	None	None	N
S/H	0.2583	likely_benign	0.2597	benign	-1.375	Destabilizing	0.859	D	0.469	neutral	None	None	None	None	N
S/I	0.173	likely_benign	0.1564	benign	-0.151	Destabilizing	0.02	N	0.447	neutral	None	None	None	None	N
S/K	0.4336	ambiguous	0.4278	ambiguous	-0.77	Destabilizing	0.104	N	0.334	neutral	None	None	None	None	N
S/L	0.1106	likely_benign	0.1056	benign	-0.151	Destabilizing	0.042	N	0.511	neutral	N	0.484389337	None	None	N
S/M	0.193	likely_benign	0.1799	benign	0.224	Stabilizing	0.497	N	0.459	neutral	None	None	None	None	N
S/N	0.1392	likely_benign	0.1368	benign	-0.87	Destabilizing	0.22	N	0.339	neutral	None	None	None	None	N
S/P	0.8964	likely_pathogenic	0.8925	pathogenic	-0.268	Destabilizing	0.301	N	0.431	neutral	N	0.498027048	None	None	N
S/Q	0.3595	ambiguous	0.3505	ambiguous	-1.153	Destabilizing	0.22	N	0.419	neutral	None	None	None	None	N
S/R	0.3143	likely_benign	0.3054	benign	-0.547	Destabilizing	0.22	N	0.451	neutral	None	None	None	None	N
S/T	0.0699	likely_benign	0.0664	benign	-0.774	Destabilizing	None	N	0.105	neutral	N	0.403801794	None	None	N
S/V	0.1731	likely_benign	0.1544	benign	-0.268	Destabilizing	None	N	0.269	neutral	None	None	None	None	N
S/W	0.275	likely_benign	0.2466	benign	-0.993	Destabilizing	0.958	D	0.527	neutral	None	None	None	None	N
S/Y	0.1729	likely_benign	0.1543	benign	-0.679	Destabilizing	0.667	D	0.515	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.