TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10094	30505;30506;30507	chr2:178702607;178702606;178702605	chr2:179567334;179567333;179567332
N2AB	9777	29554;29555;29556	chr2:178702607;178702606;178702605	chr2:179567334;179567333;179567332
N2A	8850	26773;26774;26775	chr2:178702607;178702606;178702605	chr2:179567334;179567333;179567332
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-86
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.3201
• 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
S/P	rs773164933	-0.371	0.999	None	0.721	0.406	0.42538462244	gnomAD-2.1.1	1.2E-05	None	None	None	None	N	None	0	8.69E-05	None	0	0	None	0	None	0	0	0
S/P	rs773164933	-0.371	0.999	None	0.721	0.406	0.42538462244	gnomAD-4.0.0	6.36345E-06	None	None	None	None	N	None	0	9.14495E-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
S/A	0.3158	likely_benign	0.3742	ambiguous	-0.549	Destabilizing	0.973	D	0.339	neutral	None	None	None	None	N
S/C	0.8075	likely_pathogenic	0.8258	pathogenic	-0.333	Destabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	N
S/D	0.9167	likely_pathogenic	0.9043	pathogenic	-0.296	Destabilizing	0.996	D	0.496	neutral	None	None	None	None	N
S/E	0.9358	likely_pathogenic	0.9406	pathogenic	-0.34	Destabilizing	0.996	D	0.505	neutral	None	None	None	None	N
S/F	0.9464	likely_pathogenic	0.9513	pathogenic	-0.853	Destabilizing	0.999	D	0.753	deleterious	None	None	None	None	N
S/G	0.6692	likely_pathogenic	0.6429	pathogenic	-0.757	Destabilizing	0.996	D	0.424	neutral	None	None	None	None	N
S/H	0.9222	likely_pathogenic	0.9198	pathogenic	-1.286	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
S/I	0.8921	likely_pathogenic	0.8895	pathogenic	-0.114	Destabilizing	0.998	D	0.754	deleterious	None	None	None	None	N
S/K	0.9894	likely_pathogenic	0.989	pathogenic	-0.729	Destabilizing	0.996	D	0.491	neutral	None	None	None	None	N
S/L	0.7912	likely_pathogenic	0.7809	pathogenic	-0.114	Destabilizing	0.992	D	0.576	neutral	None	None	None	None	N
S/M	0.8206	likely_pathogenic	0.8126	pathogenic	0.25	Stabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
S/N	0.7535	likely_pathogenic	0.7038	pathogenic	-0.554	Destabilizing	0.996	D	0.493	neutral	None	None	None	None	N
S/P	0.8479	likely_pathogenic	0.8454	pathogenic	-0.226	Destabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	N
S/Q	0.9412	likely_pathogenic	0.9452	pathogenic	-0.784	Destabilizing	1.0	D	0.652	neutral	None	None	None	None	N
S/R	0.9851	likely_pathogenic	0.985	pathogenic	-0.524	Destabilizing	0.999	D	0.737	prob.delet.	None	None	None	None	N
S/T	0.4407	ambiguous	0.3744	ambiguous	-0.589	Destabilizing	0.543	D	0.279	neutral	None	None	None	None	N
S/V	0.8687	likely_pathogenic	0.874	pathogenic	-0.226	Destabilizing	0.998	D	0.639	neutral	None	None	None	None	N
S/W	0.9424	likely_pathogenic	0.9427	pathogenic	-0.839	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
S/Y	0.8941	likely_pathogenic	0.89	pathogenic	-0.584	Destabilizing	0.999	D	0.749	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.