TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8839	26740;26741;26742	chr2:178714143;178714142;178714141	chr2:179578870;179578869;179578868
N2AB	8522	25789;25790;25791	chr2:178714143;178714142;178714141	chr2:179578870;179578869;179578868
N2A	7595	23008;23009;23010	chr2:178714143;178714142;178714141	chr2:179578870;179578869;179578868
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: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-74
• Domain position: 10
• Structural Position: 13
• Q(SASA): 0.2806
• 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
I/M	None	None	0.001	N	0.133	0.107	0.171388866994	gnomAD-4.0.0	1.369E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99683E-07	0	1.65717E-05
I/T	None	None	0.001	N	0.179	0.184	0.665430918054	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
I/V	None	None	None	N	0.056	0.174	0.418718287753	gnomAD-4.0.0	2.05351E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69906E-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
I/A	0.2225	likely_benign	0.2024	benign	-1.365	Destabilizing	0.025	N	0.295	neutral	None	None	None	None	N
I/C	0.5409	ambiguous	0.5096	ambiguous	-0.859	Destabilizing	0.667	D	0.353	neutral	None	None	None	None	N
I/D	0.6279	likely_pathogenic	0.5678	pathogenic	-0.536	Destabilizing	0.22	N	0.527	neutral	None	None	None	None	N
I/E	0.4216	ambiguous	0.3411	ambiguous	-0.542	Destabilizing	0.22	N	0.485	neutral	None	None	None	None	N
I/F	0.118	likely_benign	0.1128	benign	-0.909	Destabilizing	0.22	N	0.274	neutral	None	None	None	None	N
I/G	0.4397	ambiguous	0.4133	ambiguous	-1.672	Destabilizing	0.22	N	0.467	neutral	None	None	None	None	N
I/H	0.3975	ambiguous	0.3504	ambiguous	-0.87	Destabilizing	0.859	D	0.407	neutral	None	None	None	None	N
I/K	0.2576	likely_benign	0.1802	benign	-0.87	Destabilizing	0.175	N	0.469	neutral	N	0.511049476	None	None	N
I/L	0.0784	likely_benign	0.0758	benign	-0.616	Destabilizing	None	N	0.052	neutral	N	0.445861847	None	None	N
I/M	0.07	likely_benign	0.0621	benign	-0.541	Destabilizing	0.001	N	0.133	neutral	N	0.503160712	None	None	N
I/N	0.2551	likely_benign	0.2167	benign	-0.668	Destabilizing	0.497	N	0.516	neutral	None	None	None	None	N
I/P	0.7212	likely_pathogenic	0.7204	pathogenic	-0.833	Destabilizing	0.667	D	0.521	neutral	None	None	None	None	N
I/Q	0.2731	likely_benign	0.206	benign	-0.818	Destabilizing	0.667	D	0.505	neutral	None	None	None	None	N
I/R	0.1812	likely_benign	0.1287	benign	-0.339	Destabilizing	0.427	N	0.521	neutral	N	0.511396193	None	None	N
I/S	0.223	likely_benign	0.1867	benign	-1.296	Destabilizing	0.055	N	0.387	neutral	None	None	None	None	N
I/T	0.1657	likely_benign	0.1308	benign	-1.179	Destabilizing	0.001	N	0.179	neutral	N	0.498677612	None	None	N
I/V	0.0633	likely_benign	0.0644	benign	-0.833	Destabilizing	None	N	0.056	neutral	N	0.44435755	None	None	N
I/W	0.5705	likely_pathogenic	0.5398	ambiguous	-0.956	Destabilizing	0.958	D	0.417	neutral	None	None	None	None	N
I/Y	0.3527	ambiguous	0.3228	benign	-0.731	Destabilizing	0.667	D	0.437	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.