TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15406	46441;46442;46443	chr2:178620305;178620304;178620303	chr2:179485032;179485031;179485030
N2AB	13765	41518;41519;41520	chr2:178620305;178620304;178620303	chr2:179485032;179485031;179485030
N2A	12838	38737;38738;38739	chr2:178620305;178620304;178620303	chr2:179485032;179485031;179485030
N2B	6341	19246;19247;19248	chr2:178620305;178620304;178620303	chr2:179485032;179485031;179485030
Novex-1	6466	19621;19622;19623	chr2:178620305;178620304;178620303	chr2:179485032;179485031;179485030
Novex-2	6533	19822;19823;19824	chr2:178620305;178620304;178620303	chr2:179485032;179485031;179485030
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-106
• Domain position: 16
• Structural Position: 25
• Q(SASA): 0.2436
• 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
D/N	rs2058075487	None	0.989	N	0.443	0.446	0.447901950027	gnomAD-4.0.0	2.8165E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.75031E-06	0	1.71086E-05

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
D/A	0.4005	ambiguous	0.333	benign	-0.311	Destabilizing	0.939	D	0.501	neutral	N	0.483871322	None	None	N
D/C	0.9068	likely_pathogenic	0.8709	pathogenic	0.147	Stabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	N
D/E	0.2514	likely_benign	0.1963	benign	-0.591	Destabilizing	0.02	N	0.241	neutral	N	0.351267183	None	None	N
D/F	0.9241	likely_pathogenic	0.8789	pathogenic	-0.554	Destabilizing	0.998	D	0.693	prob.neutral	None	None	None	None	N
D/G	0.4461	ambiguous	0.3647	ambiguous	-0.534	Destabilizing	0.969	D	0.448	neutral	N	0.489511107	None	None	N
D/H	0.642	likely_pathogenic	0.5355	ambiguous	-0.803	Destabilizing	0.999	D	0.51	neutral	N	0.520795136	None	None	N
D/I	0.8339	likely_pathogenic	0.7538	pathogenic	0.234	Stabilizing	0.993	D	0.7	prob.neutral	None	None	None	None	N
D/K	0.6512	likely_pathogenic	0.5217	ambiguous	0.006	Stabilizing	0.91	D	0.425	neutral	None	None	None	None	N
D/L	0.7718	likely_pathogenic	0.6823	pathogenic	0.234	Stabilizing	0.986	D	0.684	prob.neutral	None	None	None	None	N
D/M	0.8865	likely_pathogenic	0.838	pathogenic	0.648	Stabilizing	0.999	D	0.689	prob.neutral	None	None	None	None	N
D/N	0.2558	likely_benign	0.2019	benign	-0.157	Destabilizing	0.989	D	0.443	neutral	N	0.517697495	None	None	N
D/P	0.9865	likely_pathogenic	0.985	pathogenic	0.076	Stabilizing	0.993	D	0.502	neutral	None	None	None	None	N
D/Q	0.507	ambiguous	0.4075	ambiguous	-0.13	Destabilizing	0.973	D	0.435	neutral	None	None	None	None	N
D/R	0.6691	likely_pathogenic	0.5418	ambiguous	-0.009	Destabilizing	0.986	D	0.619	neutral	None	None	None	None	N
D/S	0.2755	likely_benign	0.2195	benign	-0.291	Destabilizing	0.953	D	0.403	neutral	None	None	None	None	N
D/T	0.5655	likely_pathogenic	0.4642	ambiguous	-0.127	Destabilizing	0.986	D	0.448	neutral	None	None	None	None	N
D/V	0.6408	likely_pathogenic	0.5399	ambiguous	0.076	Stabilizing	0.991	D	0.683	prob.neutral	D	0.543787967	None	None	N
D/W	0.9749	likely_pathogenic	0.9612	pathogenic	-0.547	Destabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	N
D/Y	0.6419	likely_pathogenic	0.5549	ambiguous	-0.362	Destabilizing	0.999	D	0.692	prob.neutral	D	0.546337334	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.