TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1635	5128;5129;5130	chr2:178776961;178776960;178776959	chr2:179641688;179641687;179641686
N2AB	1635	5128;5129;5130	chr2:178776961;178776960;178776959	chr2:179641688;179641687;179641686
N2A	1635	5128;5129;5130	chr2:178776961;178776960;178776959	chr2:179641688;179641687;179641686
N2B	1589	4990;4991;4992	chr2:178776961;178776960;178776959	chr2:179641688;179641687;179641686
Novex-1	1589	4990;4991;4992	chr2:178776961;178776960;178776959	chr2:179641688;179641687;179641686
Novex-2	1589	4990;4991;4992	chr2:178776961;178776960;178776959	chr2:179641688;179641687;179641686
Novex-3	1635	5128;5129;5130	chr2:178776961;178776960;178776959	chr2:179641688;179641687;179641686

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-7
• Domain position: 80
• Structural Position: 162
• Q(SASA): 0.9383
• 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	rs776274777	0.016	0.999	N	0.598	0.475	0.38225645794	gnomAD-2.1.1	7.99E-06	None	None	None	None	I	None	0	5.8E-05	None	0	0	None	0	None	0	0	0
K/E	rs776274777	0.016	0.999	N	0.598	0.475	0.38225645794	gnomAD-4.0.0	3.18202E-06	None	None	None	None	I	None	0	4.57561E-05	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	0.824	likely_pathogenic	0.7217	pathogenic	0.022	Stabilizing	0.999	D	0.591	neutral	None	None	None	None	I
K/C	0.973	likely_pathogenic	0.9487	pathogenic	-0.369	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	I
K/D	0.9579	likely_pathogenic	0.9228	pathogenic	-0.287	Destabilizing	1.0	D	0.644	neutral	None	None	None	None	I
K/E	0.721	likely_pathogenic	0.5903	pathogenic	-0.303	Destabilizing	0.999	D	0.598	neutral	N	0.495801937	None	None	I
K/F	0.9869	likely_pathogenic	0.972	pathogenic	-0.334	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	I
K/G	0.909	likely_pathogenic	0.8361	pathogenic	-0.105	Destabilizing	1.0	D	0.605	neutral	None	None	None	None	I
K/H	0.7524	likely_pathogenic	0.6574	pathogenic	-0.253	Destabilizing	1.0	D	0.649	neutral	None	None	None	None	I
K/I	0.8682	likely_pathogenic	0.7714	pathogenic	0.271	Stabilizing	1.0	D	0.721	prob.delet.	N	0.513423985	None	None	I
K/L	0.8463	likely_pathogenic	0.7481	pathogenic	0.271	Stabilizing	1.0	D	0.605	neutral	None	None	None	None	I
K/M	0.7635	likely_pathogenic	0.6412	pathogenic	-0.033	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	I
K/N	0.917	likely_pathogenic	0.8485	pathogenic	0.073	Stabilizing	1.0	D	0.687	prob.neutral	N	0.509757673	None	None	I
K/P	0.9229	likely_pathogenic	0.8561	pathogenic	0.212	Stabilizing	1.0	D	0.634	neutral	None	None	None	None	I
K/Q	0.4526	ambiguous	0.3429	ambiguous	-0.081	Destabilizing	1.0	D	0.679	prob.neutral	D	0.559921488	None	None	I
K/R	0.1266	likely_benign	0.1109	benign	-0.094	Destabilizing	0.999	D	0.542	neutral	N	0.502297159	None	None	I
K/S	0.8906	likely_pathogenic	0.8104	pathogenic	-0.288	Destabilizing	0.999	D	0.62	neutral	None	None	None	None	I
K/T	0.6794	likely_pathogenic	0.5411	ambiguous	-0.188	Destabilizing	1.0	D	0.621	neutral	N	0.512818854	None	None	I
K/V	0.8132	likely_pathogenic	0.7112	pathogenic	0.212	Stabilizing	1.0	D	0.671	neutral	None	None	None	None	I
K/W	0.9828	likely_pathogenic	0.9666	pathogenic	-0.436	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	I
K/Y	0.9609	likely_pathogenic	0.9287	pathogenic	-0.079	Destabilizing	1.0	D	0.693	prob.neutral	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.