TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30053	90382;90383;90384	chr2:178552743;178552742;178552741	chr2:179417470;179417469;179417468
N2AB	28412	85459;85460;85461	chr2:178552743;178552742;178552741	chr2:179417470;179417469;179417468
N2A	27485	82678;82679;82680	chr2:178552743;178552742;178552741	chr2:179417470;179417469;179417468
N2B	20988	63187;63188;63189	chr2:178552743;178552742;178552741	chr2:179417470;179417469;179417468
Novex-1	21113	63562;63563;63564	chr2:178552743;178552742;178552741	chr2:179417470;179417469;179417468
Novex-2	21180	63763;63764;63765	chr2:178552743;178552742;178552741	chr2:179417470;179417469;179417468
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: Fn3-107
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.4681
• 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/N	rs886039117	None	0.998	N	0.687	0.33	0.207176502487	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/N	rs886039117	None	0.998	N	0.687	0.33	0.207176502487	gnomAD-4.0.0	2.56176E-06	None	None	None	None	N	None	3.38146E-05	0	None	0	0	None	0	0	0	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	0.831	likely_pathogenic	0.7654	pathogenic	-0.521	Destabilizing	0.996	D	0.609	neutral	None	None	None	None	N
K/C	0.9397	likely_pathogenic	0.9194	pathogenic	-0.713	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
K/D	0.9702	likely_pathogenic	0.9574	pathogenic	-0.447	Destabilizing	0.999	D	0.753	deleterious	None	None	None	None	N
K/E	0.7785	likely_pathogenic	0.6933	pathogenic	-0.334	Destabilizing	0.989	D	0.555	neutral	N	0.467724694	None	None	N
K/F	0.9745	likely_pathogenic	0.9642	pathogenic	-0.372	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
K/G	0.9221	likely_pathogenic	0.8779	pathogenic	-0.818	Destabilizing	0.999	D	0.68	prob.neutral	None	None	None	None	N
K/H	0.7551	likely_pathogenic	0.6978	pathogenic	-0.859	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
K/I	0.848	likely_pathogenic	0.7943	pathogenic	0.235	Stabilizing	0.999	D	0.786	deleterious	N	0.477622982	None	None	N
K/L	0.7953	likely_pathogenic	0.739	pathogenic	0.235	Stabilizing	0.999	D	0.68	prob.neutral	None	None	None	None	N
K/M	0.735	likely_pathogenic	0.6705	pathogenic	-0.253	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
K/N	0.9424	likely_pathogenic	0.9131	pathogenic	-0.533	Destabilizing	0.998	D	0.687	prob.neutral	N	0.477965377	None	None	N
K/P	0.7743	likely_pathogenic	0.7128	pathogenic	0.01	Stabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
K/Q	0.4884	ambiguous	0.3994	ambiguous	-0.497	Destabilizing	0.997	D	0.678	prob.neutral	N	0.476306892	None	None	N
K/R	0.1085	likely_benign	0.0987	benign	-0.359	Destabilizing	0.217	N	0.284	neutral	N	0.480365918	None	None	N
K/S	0.9174	likely_pathogenic	0.8732	pathogenic	-0.998	Destabilizing	0.996	D	0.641	neutral	None	None	None	None	N
K/T	0.7915	likely_pathogenic	0.7081	pathogenic	-0.693	Destabilizing	0.998	D	0.731	prob.delet.	N	0.519326951	None	None	N
K/V	0.7862	likely_pathogenic	0.721	pathogenic	0.01	Stabilizing	0.999	D	0.751	deleterious	None	None	None	None	N
K/W	0.9709	likely_pathogenic	0.9604	pathogenic	-0.387	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
K/Y	0.9365	likely_pathogenic	0.9167	pathogenic	-0.091	Destabilizing	1.0	D	0.78	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.