TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33345	100258;100259;100260	chr2:178537076;178537075;178537074	chr2:179401803;179401802;179401801
N2AB	31704	95335;95336;95337	chr2:178537076;178537075;178537074	chr2:179401803;179401802;179401801
N2A	30777	92554;92555;92556	chr2:178537076;178537075;178537074	chr2:179401803;179401802;179401801
N2B	24280	73063;73064;73065	chr2:178537076;178537075;178537074	chr2:179401803;179401802;179401801
Novex-1	24405	73438;73439;73440	chr2:178537076;178537075;178537074	chr2:179401803;179401802;179401801
Novex-2	24472	73639;73640;73641	chr2:178537076;178537075;178537074	chr2:179401803;179401802;179401801
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Fn3-130
• Domain position: 56
• Structural Position: 75
• Q(SASA): 0.2852
• 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
A/V	rs1559064081	None	0.565	N	0.469	0.214	0.410868550352	gnomAD-4.0.0	1.5931E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86064E-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
A/C	0.5994	likely_pathogenic	0.6013	pathogenic	-0.757	Destabilizing	0.996	D	0.541	neutral	None	None	None	None	N
A/D	0.6988	likely_pathogenic	0.7671	pathogenic	-0.167	Destabilizing	0.722	D	0.644	neutral	N	0.463625597	None	None	N
A/E	0.6698	likely_pathogenic	0.7424	pathogenic	-0.318	Destabilizing	0.775	D	0.579	neutral	None	None	None	None	N
A/F	0.6192	likely_pathogenic	0.6682	pathogenic	-0.822	Destabilizing	0.961	D	0.689	prob.neutral	None	None	None	None	N
A/G	0.2487	likely_benign	0.2466	benign	-0.16	Destabilizing	0.349	N	0.495	neutral	N	0.453256674	None	None	N
A/H	0.7457	likely_pathogenic	0.8016	pathogenic	-0.205	Destabilizing	0.996	D	0.694	prob.neutral	None	None	None	None	N
A/I	0.6813	likely_pathogenic	0.6943	pathogenic	-0.307	Destabilizing	0.923	D	0.599	neutral	None	None	None	None	N
A/K	0.8434	likely_pathogenic	0.8966	pathogenic	-0.325	Destabilizing	0.775	D	0.585	neutral	None	None	None	None	N
A/L	0.4599	ambiguous	0.4936	ambiguous	-0.307	Destabilizing	0.633	D	0.545	neutral	None	None	None	None	N
A/M	0.5236	ambiguous	0.52	ambiguous	-0.353	Destabilizing	0.989	D	0.603	neutral	None	None	None	None	N
A/N	0.4628	ambiguous	0.4901	ambiguous	-0.107	Destabilizing	0.923	D	0.649	neutral	None	None	None	None	N
A/P	0.8577	likely_pathogenic	0.9062	pathogenic	-0.225	Destabilizing	0.949	D	0.598	neutral	N	0.476090675	None	None	N
A/Q	0.6037	likely_pathogenic	0.6608	pathogenic	-0.359	Destabilizing	0.961	D	0.62	neutral	None	None	None	None	N
A/R	0.737	likely_pathogenic	0.8265	pathogenic	0.046	Stabilizing	0.923	D	0.628	neutral	None	None	None	None	N
A/S	0.0997	likely_benign	0.0946	benign	-0.322	Destabilizing	0.014	N	0.189	neutral	N	0.401171628	None	None	N
A/T	0.1719	likely_benign	0.1619	benign	-0.393	Destabilizing	0.008	N	0.337	neutral	N	0.407214953	None	None	N
A/V	0.3796	ambiguous	0.3754	ambiguous	-0.225	Destabilizing	0.565	D	0.469	neutral	N	0.453795392	None	None	N
A/W	0.9146	likely_pathogenic	0.9465	pathogenic	-0.936	Destabilizing	0.996	D	0.759	deleterious	None	None	None	None	N
A/Y	0.7527	likely_pathogenic	0.8062	pathogenic	-0.585	Destabilizing	0.987	D	0.691	prob.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.