TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32225	96898;96899;96900	chr2:178543300;178543299;178543298	chr2:179408027;179408026;179408025
N2AB	30584	91975;91976;91977	chr2:178543300;178543299;178543298	chr2:179408027;179408026;179408025
N2A	29657	89194;89195;89196	chr2:178543300;178543299;178543298	chr2:179408027;179408026;179408025
N2B	23160	69703;69704;69705	chr2:178543300;178543299;178543298	chr2:179408027;179408026;179408025
Novex-1	23285	70078;70079;70080	chr2:178543300;178543299;178543298	chr2:179408027;179408026;179408025
Novex-2	23352	70279;70280;70281	chr2:178543300;178543299;178543298	chr2:179408027;179408026;179408025
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: Fn3-123
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.7101
• Predicted PPI site: I

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	rs749032092	-0.612	0.997	N	0.614	0.389	None	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
K/E	rs749032092	-0.612	0.997	N	0.614	0.389	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/E	rs749032092	-0.612	0.997	N	0.614	0.389	None	gnomAD-4.0.0	6.57367E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.47033E-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	0.7617	likely_pathogenic	0.7182	pathogenic	-0.879	Destabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	I
K/C	0.9125	likely_pathogenic	0.8965	pathogenic	-1.021	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	I
K/D	0.9303	likely_pathogenic	0.9225	pathogenic	-0.901	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
K/E	0.6255	likely_pathogenic	0.5743	pathogenic	-0.738	Destabilizing	0.997	D	0.614	neutral	N	0.493583144	None	None	I
K/F	0.9497	likely_pathogenic	0.9433	pathogenic	-0.544	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	I
K/G	0.8474	likely_pathogenic	0.8346	pathogenic	-1.221	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
K/H	0.6541	likely_pathogenic	0.6358	pathogenic	-1.119	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
K/I	0.7552	likely_pathogenic	0.7228	pathogenic	0.029	Stabilizing	0.992	D	0.783	deleterious	N	0.482395922	None	None	I
K/L	0.6679	likely_pathogenic	0.6397	pathogenic	0.029	Stabilizing	0.994	D	0.747	deleterious	None	None	None	None	I
K/M	0.5658	likely_pathogenic	0.5271	ambiguous	-0.424	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
K/N	0.8466	likely_pathogenic	0.8327	pathogenic	-1.025	Destabilizing	1.0	D	0.753	deleterious	N	0.473686189	None	None	I
K/P	0.6543	likely_pathogenic	0.629	pathogenic	-0.249	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	I
K/Q	0.3827	ambiguous	0.3403	ambiguous	-0.928	Destabilizing	0.998	D	0.737	prob.delet.	N	0.506475084	None	None	I
K/R	0.1269	likely_benign	0.1194	benign	-0.575	Destabilizing	0.996	D	0.602	neutral	N	0.491948348	None	None	I
K/S	0.8627	likely_pathogenic	0.8447	pathogenic	-1.514	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	I
K/T	0.6641	likely_pathogenic	0.6284	pathogenic	-1.144	Destabilizing	0.999	D	0.783	deleterious	N	0.516364003	None	None	I
K/V	0.7142	likely_pathogenic	0.6782	pathogenic	-0.249	Destabilizing	0.996	D	0.781	deleterious	None	None	None	None	I
K/W	0.9393	likely_pathogenic	0.9287	pathogenic	-0.535	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	I
K/Y	0.857	likely_pathogenic	0.8461	pathogenic	-0.267	Destabilizing	0.999	D	0.778	deleterious	None	None	None	None	I

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.