TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21438	64537;64538;64539	chr2:178586589;178586588;178586587	chr2:179451316;179451315;179451314
N2AB	19797	59614;59615;59616	chr2:178586589;178586588;178586587	chr2:179451316;179451315;179451314
N2A	18870	56833;56834;56835	chr2:178586589;178586588;178586587	chr2:179451316;179451315;179451314
N2B	12373	37342;37343;37344	chr2:178586589;178586588;178586587	chr2:179451316;179451315;179451314
Novex-1	12498	37717;37718;37719	chr2:178586589;178586588;178586587	chr2:179451316;179451315;179451314
Novex-2	12565	37918;37919;37920	chr2:178586589;178586588;178586587	chr2:179451316;179451315;179451314
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: Fn3-43
• Domain position: 73
• Structural Position: 105
• Q(SASA): 0.4052
• 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
K/E	None	None	0.896	N	0.574	0.269	0.245660935333	gnomAD-4.0.0	1.59257E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86094E-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
K/A	0.4739	ambiguous	0.5026	ambiguous	-1.541	Destabilizing	0.919	D	0.565	neutral	None	None	None	None	N
K/C	0.5535	ambiguous	0.5541	ambiguous	-1.537	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
K/D	0.9091	likely_pathogenic	0.9183	pathogenic	-1.864	Destabilizing	0.952	D	0.616	neutral	None	None	None	None	N
K/E	0.4824	ambiguous	0.4906	ambiguous	-1.57	Destabilizing	0.896	D	0.574	neutral	N	0.436265637	None	None	N
K/F	0.7401	likely_pathogenic	0.7566	pathogenic	-0.614	Destabilizing	0.996	D	0.726	prob.delet.	None	None	None	None	N
K/G	0.7214	likely_pathogenic	0.7432	pathogenic	-2.011	Highly Destabilizing	0.851	D	0.589	neutral	None	None	None	None	N
K/H	0.2665	likely_benign	0.2843	benign	-1.914	Destabilizing	0.988	D	0.672	neutral	None	None	None	None	N
K/I	0.3444	ambiguous	0.3573	ambiguous	-0.203	Destabilizing	0.984	D	0.73	prob.delet.	N	0.472074508	None	None	N
K/L	0.3895	ambiguous	0.3976	ambiguous	-0.203	Destabilizing	0.919	D	0.625	neutral	None	None	None	None	N
K/M	0.2917	likely_benign	0.3073	benign	-0.637	Destabilizing	0.999	D	0.648	neutral	None	None	None	None	N
K/N	0.7232	likely_pathogenic	0.7541	pathogenic	-1.855	Destabilizing	0.059	N	0.453	neutral	N	0.488291968	None	None	N
K/P	0.9842	likely_pathogenic	0.9868	pathogenic	-0.63	Destabilizing	0.996	D	0.673	neutral	None	None	None	None	N
K/Q	0.1562	likely_benign	0.1651	benign	-1.499	Destabilizing	0.968	D	0.615	neutral	N	0.447157421	None	None	N
K/R	0.0764	likely_benign	0.0757	benign	-1.2	Destabilizing	0.026	N	0.344	neutral	N	0.418682741	None	None	N
K/S	0.5675	likely_pathogenic	0.6017	pathogenic	-2.37	Highly Destabilizing	0.851	D	0.53	neutral	None	None	None	None	N
K/T	0.2225	likely_benign	0.2465	benign	-1.833	Destabilizing	0.896	D	0.594	neutral	N	0.438324507	None	None	N
K/V	0.3053	likely_benign	0.3215	benign	-0.63	Destabilizing	0.988	D	0.694	prob.neutral	None	None	None	None	N
K/W	0.7284	likely_pathogenic	0.733	pathogenic	-0.674	Destabilizing	0.999	D	0.657	neutral	None	None	None	None	N
K/Y	0.5917	likely_pathogenic	0.6041	pathogenic	-0.358	Destabilizing	0.996	D	0.715	prob.delet.	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.