TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16747	50464;50465;50466	chr2:178612286;178612285;178612284	chr2:179477013;179477012;179477011
N2AB	15106	45541;45542;45543	chr2:178612286;178612285;178612284	chr2:179477013;179477012;179477011
N2A	14179	42760;42761;42762	chr2:178612286;178612285;178612284	chr2:179477013;179477012;179477011
N2B	7682	23269;23270;23271	chr2:178612286;178612285;178612284	chr2:179477013;179477012;179477011
Novex-1	7807	23644;23645;23646	chr2:178612286;178612285;178612284	chr2:179477013;179477012;179477011
Novex-2	7874	23845;23846;23847	chr2:178612286;178612285;178612284	chr2:179477013;179477012;179477011
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-9
• Domain position: 97
• Structural Position: 132
• Q(SASA): 0.8249
• 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
D/G	rs745559631	-0.083	1.0	D	0.766	0.399	0.391000631824	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	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
D/A	0.9083	likely_pathogenic	0.974	pathogenic	-0.205	Destabilizing	1.0	D	0.707	prob.delet.	N	0.496777116	None	None	N
D/C	0.9895	likely_pathogenic	0.9968	pathogenic	0.121	Stabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
D/E	0.7557	likely_pathogenic	0.896	pathogenic	-0.328	Destabilizing	0.999	D	0.439	neutral	N	0.493794379	None	None	N
D/F	0.9903	likely_pathogenic	0.9972	pathogenic	-0.277	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
D/G	0.8201	likely_pathogenic	0.9462	pathogenic	-0.373	Destabilizing	1.0	D	0.766	deleterious	D	0.524240019	None	None	N
D/H	0.9643	likely_pathogenic	0.9881	pathogenic	-0.084	Destabilizing	1.0	D	0.844	deleterious	D	0.565870176	None	None	N
D/I	0.9818	likely_pathogenic	0.996	pathogenic	0.18	Stabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
D/K	0.9773	likely_pathogenic	0.9936	pathogenic	0.408	Stabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
D/L	0.9668	likely_pathogenic	0.9928	pathogenic	0.18	Stabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
D/M	0.9912	likely_pathogenic	0.9981	pathogenic	0.305	Stabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
D/N	0.563	ambiguous	0.7972	pathogenic	0.176	Stabilizing	1.0	D	0.751	deleterious	N	0.502709338	None	None	N
D/P	0.9766	likely_pathogenic	0.9943	pathogenic	0.073	Stabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
D/Q	0.9709	likely_pathogenic	0.9924	pathogenic	0.18	Stabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
D/R	0.9822	likely_pathogenic	0.9948	pathogenic	0.524	Stabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
D/S	0.7869	likely_pathogenic	0.9267	pathogenic	0.079	Stabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
D/T	0.9343	likely_pathogenic	0.9846	pathogenic	0.206	Stabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
D/V	0.9379	likely_pathogenic	0.9843	pathogenic	0.073	Stabilizing	1.0	D	0.739	deleterious	D	0.554086724	None	None	N
D/W	0.9976	likely_pathogenic	0.9993	pathogenic	-0.19	Destabilizing	1.0	D	0.738	deleterious	None	None	None	None	N
D/Y	0.9122	likely_pathogenic	0.9734	pathogenic	-0.046	Destabilizing	1.0	D	0.762	deleterious	N	0.501479942	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.