TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29189	87790;87791;87792	chr2:178557789;178557788;178557787	chr2:179422516;179422515;179422514
N2AB	27548	82867;82868;82869	chr2:178557789;178557788;178557787	chr2:179422516;179422515;179422514
N2A	26621	80086;80087;80088	chr2:178557789;178557788;178557787	chr2:179422516;179422515;179422514
N2B	20124	60595;60596;60597	chr2:178557789;178557788;178557787	chr2:179422516;179422515;179422514
Novex-1	20249	60970;60971;60972	chr2:178557789;178557788;178557787	chr2:179422516;179422515;179422514
Novex-2	20316	61171;61172;61173	chr2:178557789;178557788;178557787	chr2:179422516;179422515;179422514
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: Fn3-100
• Domain position: 53
• Structural Position: 69
• Q(SASA): 0.1468
• 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/F	rs1319240179	-0.653	0.999	N	0.74	0.452	0.791748981498	gnomAD-4.0.0	7.95499E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	7.16353E-05	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	0.1242	likely_benign	0.1234	benign	-0.495	Destabilizing	0.543	D	0.273	neutral	N	0.482715577	None	None	N
S/C	0.1433	likely_benign	0.1509	benign	-0.446	Destabilizing	1.0	D	0.721	prob.delet.	N	0.482906582	None	None	N
S/D	0.9589	likely_pathogenic	0.9647	pathogenic	-0.082	Destabilizing	0.996	D	0.596	neutral	None	None	None	None	N
S/E	0.9704	likely_pathogenic	0.9724	pathogenic	-0.093	Destabilizing	0.996	D	0.557	neutral	None	None	None	None	N
S/F	0.6892	likely_pathogenic	0.6832	pathogenic	-0.712	Destabilizing	0.999	D	0.74	deleterious	N	0.504516329	None	None	N
S/G	0.2527	likely_benign	0.2737	benign	-0.735	Destabilizing	0.992	D	0.474	neutral	None	None	None	None	N
S/H	0.8627	likely_pathogenic	0.867	pathogenic	-1.226	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
S/I	0.6258	likely_pathogenic	0.6292	pathogenic	0.026	Stabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	N
S/K	0.9892	likely_pathogenic	0.9896	pathogenic	-0.644	Destabilizing	0.996	D	0.553	neutral	None	None	None	None	N
S/L	0.2138	likely_benign	0.2184	benign	0.026	Stabilizing	0.992	D	0.591	neutral	None	None	None	None	N
S/M	0.4122	ambiguous	0.407	ambiguous	0.167	Stabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
S/N	0.5498	ambiguous	0.6008	pathogenic	-0.609	Destabilizing	1.0	D	0.611	neutral	None	None	None	None	N
S/P	0.939	likely_pathogenic	0.9665	pathogenic	-0.113	Destabilizing	0.998	D	0.72	prob.delet.	N	0.480905119	None	None	N
S/Q	0.9209	likely_pathogenic	0.9216	pathogenic	-0.728	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
S/R	0.9799	likely_pathogenic	0.9813	pathogenic	-0.548	Destabilizing	0.999	D	0.736	prob.delet.	None	None	None	None	N
S/T	0.183	likely_benign	0.1847	benign	-0.606	Destabilizing	0.989	D	0.463	neutral	N	0.46449225	None	None	N
S/V	0.4839	ambiguous	0.4887	ambiguous	-0.113	Destabilizing	0.998	D	0.653	neutral	None	None	None	None	N
S/W	0.8211	likely_pathogenic	0.8238	pathogenic	-0.728	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
S/Y	0.6551	likely_pathogenic	0.6582	pathogenic	-0.443	Destabilizing	0.999	D	0.733	prob.delet.	N	0.469321777	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.