TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27138	81637;81638;81639	chr2:178564720;178564719;178564718	chr2:179429447;179429446;179429445
N2AB	25497	76714;76715;76716	chr2:178564720;178564719;178564718	chr2:179429447;179429446;179429445
N2A	24570	73933;73934;73935	chr2:178564720;178564719;178564718	chr2:179429447;179429446;179429445
N2B	18073	54442;54443;54444	chr2:178564720;178564719;178564718	chr2:179429447;179429446;179429445
Novex-1	18198	54817;54818;54819	chr2:178564720;178564719;178564718	chr2:179429447;179429446;179429445
Novex-2	18265	55018;55019;55020	chr2:178564720;178564719;178564718	chr2:179429447;179429446;179429445
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: Fn3-85
• Domain position: 67
• Structural Position: 98
• Q(SASA): 0.5693
• 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/H	None	None	0.901	N	0.479	0.221	0.224531998449	gnomAD-4.0.0	2.05333E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69883E-06	0	0
D/Y	rs1336363874	None	0.018	N	0.354	0.278	0.435590266561	gnomAD-4.0.0	6.84443E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99609E-07	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
D/A	0.1164	likely_benign	0.1088	benign	-0.306	Destabilizing	0.565	D	0.421	neutral	N	0.459027853	None	None	N
D/C	0.4499	ambiguous	0.4243	ambiguous	-0.106	Destabilizing	0.996	D	0.577	neutral	None	None	None	None	N
D/E	0.0659	likely_benign	0.0644	benign	-0.357	Destabilizing	0.003	N	0.107	neutral	N	0.353321753	None	None	N
D/F	0.4681	ambiguous	0.4545	ambiguous	0.227	Stabilizing	0.858	D	0.529	neutral	None	None	None	None	N
D/G	0.1685	likely_benign	0.1633	benign	-0.597	Destabilizing	0.722	D	0.387	neutral	N	0.466836108	None	None	N
D/H	0.2083	likely_benign	0.1969	benign	0.419	Stabilizing	0.901	D	0.479	neutral	N	0.462222874	None	None	N
D/I	0.1647	likely_benign	0.157	benign	0.441	Stabilizing	0.923	D	0.541	neutral	None	None	None	None	N
D/K	0.2236	likely_benign	0.2129	benign	0.378	Stabilizing	0.633	D	0.388	neutral	None	None	None	None	N
D/L	0.2125	likely_benign	0.1999	benign	0.441	Stabilizing	0.858	D	0.451	neutral	None	None	None	None	N
D/M	0.331	likely_benign	0.3145	benign	0.537	Stabilizing	0.996	D	0.535	neutral	None	None	None	None	N
D/N	0.0987	likely_benign	0.0966	benign	-0.342	Destabilizing	0.722	D	0.43	neutral	N	0.418701383	None	None	N
D/P	0.7448	likely_pathogenic	0.6926	pathogenic	0.216	Stabilizing	0.961	D	0.461	neutral	None	None	None	None	N
D/Q	0.1666	likely_benign	0.1582	benign	-0.212	Destabilizing	0.633	D	0.401	neutral	None	None	None	None	N
D/R	0.2819	likely_benign	0.2662	benign	0.668	Stabilizing	0.923	D	0.481	neutral	None	None	None	None	N
D/S	0.0979	likely_benign	0.0939	benign	-0.446	Destabilizing	0.633	D	0.349	neutral	None	None	None	None	N
D/T	0.126	likely_benign	0.122	benign	-0.186	Destabilizing	0.775	D	0.428	neutral	None	None	None	None	N
D/V	0.0974	likely_benign	0.0924	benign	0.216	Stabilizing	0.901	D	0.451	neutral	N	0.433612121	None	None	N
D/W	0.8046	likely_pathogenic	0.7872	pathogenic	0.501	Stabilizing	0.989	D	0.567	neutral	None	None	None	None	N
D/Y	0.1802	likely_benign	0.1745	benign	0.528	Stabilizing	0.018	N	0.354	neutral	N	0.497239525	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.