TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7264	22015;22016;22017	chr2:178723217;178723216;178723215	chr2:179587944;179587943;179587942
N2AB	6947	21064;21065;21066	chr2:178723217;178723216;178723215	chr2:179587944;179587943;179587942
N2A	6020	18283;18284;18285	chr2:178723217;178723216;178723215	chr2:179587944;179587943;179587942
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: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-57
• Domain position: 35
• Structural Position: 49
• Q(SASA): 0.2986
• 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
K/E	None	None	0.002	N	0.208	0.146	0.136095386433	gnomAD-4.0.0	6.84315E-07	None	None	None	None	N	None	0	0	None	0	2.52054E-05	None	0	0	0	0	0
K/Q	rs776072028	-0.99	0.213	N	0.464	0.085	0.0716867268079	gnomAD-2.1.1	1.07E-05	None	None	None	None	N	None	4.14E-05	0	None	0	0	None	0	None	0	1.57E-05	0
K/Q	rs776072028	-0.99	0.213	N	0.464	0.085	0.0716867268079	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	2.94E-05	0	0
K/Q	rs776072028	-0.99	0.213	N	0.464	0.085	0.0716867268079	gnomAD-4.0.0	1.23958E-05	None	None	None	None	N	None	4.00555E-05	0	None	0	0	None	0	0	1.44108E-05	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
K/A	0.5291	ambiguous	0.5597	ambiguous	-0.904	Destabilizing	0.228	N	0.463	neutral	None	None	None	None	N
K/C	0.7082	likely_pathogenic	0.7223	pathogenic	-1.324	Destabilizing	0.983	D	0.604	neutral	None	None	None	None	N
K/D	0.8014	likely_pathogenic	0.815	pathogenic	-0.986	Destabilizing	0.264	N	0.513	neutral	None	None	None	None	N
K/E	0.1883	likely_benign	0.2057	benign	-0.841	Destabilizing	0.002	N	0.208	neutral	N	0.472639364	None	None	N
K/F	0.6525	likely_pathogenic	0.6741	pathogenic	-0.678	Destabilizing	0.002	N	0.475	neutral	None	None	None	None	N
K/G	0.6169	likely_pathogenic	0.6447	pathogenic	-1.274	Destabilizing	0.418	N	0.559	neutral	None	None	None	None	N
K/H	0.3331	likely_benign	0.3379	benign	-1.604	Destabilizing	0.002	N	0.273	neutral	None	None	None	None	N
K/I	0.3467	ambiguous	0.3808	ambiguous	0.069	Stabilizing	0.655	D	0.619	neutral	N	0.481912208	None	None	N
K/L	0.3118	likely_benign	0.3278	benign	0.069	Stabilizing	0.264	N	0.553	neutral	None	None	None	None	N
K/M	0.1786	likely_benign	0.197	benign	-0.109	Destabilizing	0.94	D	0.561	neutral	None	None	None	None	N
K/N	0.5038	ambiguous	0.5259	ambiguous	-1.046	Destabilizing	0.351	N	0.402	neutral	N	0.507194655	None	None	N
K/P	0.9859	likely_pathogenic	0.9872	pathogenic	-0.228	Destabilizing	0.836	D	0.585	neutral	None	None	None	None	N
K/Q	0.1202	likely_benign	0.1264	benign	-1.138	Destabilizing	0.213	N	0.464	neutral	N	0.460248857	None	None	N
K/R	0.0801	likely_benign	0.0802	benign	-0.817	Destabilizing	0.002	N	0.274	neutral	N	0.482528284	None	None	N
K/S	0.5091	ambiguous	0.5451	ambiguous	-1.678	Destabilizing	0.418	N	0.415	neutral	None	None	None	None	N
K/T	0.2364	likely_benign	0.2685	benign	-1.323	Destabilizing	0.351	N	0.487	neutral	N	0.43048331	None	None	N
K/V	0.3725	ambiguous	0.3974	ambiguous	-0.228	Destabilizing	0.418	N	0.551	neutral	None	None	None	None	N
K/W	0.6643	likely_pathogenic	0.687	pathogenic	-0.583	Destabilizing	0.983	D	0.599	neutral	None	None	None	None	N
K/Y	0.5299	ambiguous	0.5342	ambiguous	-0.203	Destabilizing	0.01	N	0.449	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.