TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17977	54154;54155;54156	chr2:178605248;178605247;178605246	chr2:179469975;179469974;179469973
N2AB	16336	49231;49232;49233	chr2:178605248;178605247;178605246	chr2:179469975;179469974;179469973
N2A	15409	46450;46451;46452	chr2:178605248;178605247;178605246	chr2:179469975;179469974;179469973
N2B	8912	26959;26960;26961	chr2:178605248;178605247;178605246	chr2:179469975;179469974;179469973
Novex-1	9037	27334;27335;27336	chr2:178605248;178605247;178605246	chr2:179469975;179469974;179469973
Novex-2	9104	27535;27536;27537	chr2:178605248;178605247;178605246	chr2:179469975;179469974;179469973
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: Ig-114
• Domain position: 10
• Structural Position: 14
• Q(SASA): 0.343
• 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	None	None	0.912	N	0.351	0.255	0.239305524855	gnomAD-4.0.0	1.60552E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.87974E-06	0	0
K/Q	None	None	0.947	N	0.385	0.254	0.263140351381	gnomAD-4.0.0	6.86935E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.01656E-07	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	0.4743	ambiguous	0.5927	pathogenic	-0.4	Destabilizing	0.737	D	0.353	neutral	None	None	None	None	N
K/C	0.7405	likely_pathogenic	0.8116	pathogenic	-0.669	Destabilizing	0.998	D	0.364	neutral	None	None	None	None	N
K/D	0.8445	likely_pathogenic	0.8894	pathogenic	0.195	Stabilizing	0.932	D	0.419	neutral	None	None	None	None	N
K/E	0.4396	ambiguous	0.4981	ambiguous	0.296	Stabilizing	0.837	D	0.317	neutral	N	0.443109543	None	None	N
K/F	0.841	likely_pathogenic	0.8866	pathogenic	-0.221	Destabilizing	0.98	D	0.404	neutral	None	None	None	None	N
K/G	0.7163	likely_pathogenic	0.8066	pathogenic	-0.705	Destabilizing	0.932	D	0.392	neutral	None	None	None	None	N
K/H	0.3789	ambiguous	0.4429	ambiguous	-0.742	Destabilizing	0.993	D	0.382	neutral	None	None	None	None	N
K/I	0.4028	ambiguous	0.4705	ambiguous	0.366	Stabilizing	0.064	N	0.234	neutral	N	0.411213343	None	None	N
K/L	0.4675	ambiguous	0.5256	ambiguous	0.366	Stabilizing	0.584	D	0.348	neutral	None	None	None	None	N
K/M	0.3112	likely_benign	0.3647	ambiguous	-0.057	Destabilizing	0.98	D	0.379	neutral	None	None	None	None	N
K/N	0.6592	likely_pathogenic	0.7412	pathogenic	-0.329	Destabilizing	0.912	D	0.351	neutral	N	0.462314167	None	None	N
K/P	0.8336	likely_pathogenic	0.8842	pathogenic	0.14	Stabilizing	0.993	D	0.421	neutral	None	None	None	None	N
K/Q	0.209	likely_benign	0.2501	benign	-0.338	Destabilizing	0.947	D	0.385	neutral	N	0.460447297	None	None	N
K/R	0.0926	likely_benign	0.0952	benign	-0.238	Destabilizing	0.016	N	0.196	neutral	N	0.423622493	None	None	N
K/S	0.5617	ambiguous	0.6895	pathogenic	-0.955	Destabilizing	0.773	D	0.296	neutral	None	None	None	None	N
K/T	0.2041	likely_benign	0.2651	benign	-0.655	Destabilizing	0.064	N	0.195	neutral	N	0.419176678	None	None	N
K/V	0.3537	ambiguous	0.426	ambiguous	0.14	Stabilizing	0.037	N	0.166	neutral	None	None	None	None	N
K/W	0.8262	likely_pathogenic	0.8689	pathogenic	-0.157	Destabilizing	0.998	D	0.438	neutral	None	None	None	None	N
K/Y	0.7449	likely_pathogenic	0.8075	pathogenic	0.148	Stabilizing	0.993	D	0.38	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.