TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25343	76252;76253;76254	chr2:178570105;178570104;178570103	chr2:179434832;179434831;179434830
N2AB	23702	71329;71330;71331	chr2:178570105;178570104;178570103	chr2:179434832;179434831;179434830
N2A	22775	68548;68549;68550	chr2:178570105;178570104;178570103	chr2:179434832;179434831;179434830
N2B	16278	49057;49058;49059	chr2:178570105;178570104;178570103	chr2:179434832;179434831;179434830
Novex-1	16403	49432;49433;49434	chr2:178570105;178570104;178570103	chr2:179434832;179434831;179434830
Novex-2	16470	49633;49634;49635	chr2:178570105;178570104;178570103	chr2:179434832;179434831;179434830
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: Fn3-72
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.2126
• 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	rs727504596	-2.253	0.944	N	0.725	0.456	0.348764635752	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
K/E	rs727504596	-2.253	0.944	N	0.725	0.456	0.348764635752	gnomAD-4.0.0	4.7903E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39757E-06	0	1.65695E-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
K/A	0.9857	likely_pathogenic	0.9836	pathogenic	-1.45	Destabilizing	0.916	D	0.697	prob.neutral	None	None	None	None	N
K/C	0.9515	likely_pathogenic	0.9476	pathogenic	-1.465	Destabilizing	0.999	D	0.833	deleterious	None	None	None	None	N
K/D	0.9982	likely_pathogenic	0.9981	pathogenic	-2.178	Highly Destabilizing	0.996	D	0.812	deleterious	None	None	None	None	N
K/E	0.9707	likely_pathogenic	0.9646	pathogenic	-1.845	Destabilizing	0.944	D	0.725	prob.delet.	N	0.492119612	None	None	N
K/F	0.9909	likely_pathogenic	0.988	pathogenic	-0.648	Destabilizing	0.975	D	0.857	deleterious	None	None	None	None	N
K/G	0.9872	likely_pathogenic	0.9844	pathogenic	-1.961	Destabilizing	0.987	D	0.781	deleterious	None	None	None	None	N
K/H	0.8637	likely_pathogenic	0.8434	pathogenic	-1.768	Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
K/I	0.9526	likely_pathogenic	0.952	pathogenic	0.017	Stabilizing	0.935	D	0.836	deleterious	N	0.467708254	None	None	N
K/L	0.9149	likely_pathogenic	0.9084	pathogenic	0.017	Stabilizing	0.653	D	0.727	prob.delet.	None	None	None	None	N
K/M	0.8153	likely_pathogenic	0.7923	pathogenic	-0.33	Destabilizing	0.693	D	0.613	neutral	None	None	None	None	N
K/N	0.991	likely_pathogenic	0.9892	pathogenic	-2.013	Highly Destabilizing	0.983	D	0.799	deleterious	N	0.518617658	None	None	N
K/P	0.9994	likely_pathogenic	0.9994	pathogenic	-0.454	Destabilizing	0.996	D	0.821	deleterious	None	None	None	None	N
K/Q	0.7223	likely_pathogenic	0.7016	pathogenic	-1.569	Destabilizing	0.983	D	0.788	deleterious	N	0.485536247	None	None	N
K/R	0.1281	likely_benign	0.1164	benign	-1.003	Destabilizing	0.944	D	0.703	prob.neutral	N	0.456123621	None	None	N
K/S	0.9901	likely_pathogenic	0.9891	pathogenic	-2.502	Highly Destabilizing	0.916	D	0.711	prob.delet.	None	None	None	None	N
K/T	0.9623	likely_pathogenic	0.962	pathogenic	-1.897	Destabilizing	0.967	D	0.771	deleterious	N	0.496777194	None	None	N
K/V	0.9339	likely_pathogenic	0.9326	pathogenic	-0.454	Destabilizing	0.845	D	0.765	deleterious	None	None	None	None	N
K/W	0.9819	likely_pathogenic	0.9785	pathogenic	-0.75	Destabilizing	0.999	D	0.813	deleterious	None	None	None	None	N
K/Y	0.9521	likely_pathogenic	0.9387	pathogenic	-0.398	Destabilizing	0.987	D	0.841	deleterious	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.