TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30038	90337;90338;90339	chr2:178552788;178552787;178552786	chr2:179417515;179417514;179417513
N2AB	28397	85414;85415;85416	chr2:178552788;178552787;178552786	chr2:179417515;179417514;179417513
N2A	27470	82633;82634;82635	chr2:178552788;178552787;178552786	chr2:179417515;179417514;179417513
N2B	20973	63142;63143;63144	chr2:178552788;178552787;178552786	chr2:179417515;179417514;179417513
Novex-1	21098	63517;63518;63519	chr2:178552788;178552787;178552786	chr2:179417515;179417514;179417513
Novex-2	21165	63718;63719;63720	chr2:178552788;178552787;178552786	chr2:179417515;179417514;179417513
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Fn3-107
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.3124
• 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/L	rs1035231480	None	0.001	N	0.243	0.088	0.375861065471	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.93751E-06	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	0.0711	likely_benign	0.0725	benign	-0.69	Destabilizing	0.001	N	0.081	neutral	N	0.45595305	None	None	N
S/C	0.0925	likely_benign	0.0943	benign	-0.413	Destabilizing	0.836	D	0.471	neutral	None	None	None	None	N
S/D	0.4279	ambiguous	0.3871	ambiguous	0.211	Stabilizing	0.129	N	0.271	neutral	None	None	None	None	N
S/E	0.4133	ambiguous	0.3804	ambiguous	0.212	Stabilizing	0.004	N	0.121	neutral	None	None	None	None	N
S/F	0.1449	likely_benign	0.1381	benign	-0.984	Destabilizing	0.264	N	0.598	neutral	None	None	None	None	N
S/G	0.1171	likely_benign	0.1102	benign	-0.928	Destabilizing	0.129	N	0.265	neutral	None	None	None	None	N
S/H	0.2508	likely_benign	0.2397	benign	-1.359	Destabilizing	0.94	D	0.465	neutral	None	None	None	None	N
S/I	0.1153	likely_benign	0.1166	benign	-0.168	Destabilizing	0.129	N	0.401	neutral	None	None	None	None	N
S/K	0.5048	ambiguous	0.4717	ambiguous	-0.489	Destabilizing	0.228	N	0.267	neutral	None	None	None	None	N
S/L	0.079	likely_benign	0.079	benign	-0.168	Destabilizing	0.001	N	0.243	neutral	N	0.472269296	None	None	N
S/M	0.1484	likely_benign	0.1569	benign	-0.014	Destabilizing	0.716	D	0.455	neutral	None	None	None	None	N
S/N	0.143	likely_benign	0.1375	benign	-0.473	Destabilizing	0.418	N	0.281	neutral	None	None	None	None	N
S/P	0.8422	likely_pathogenic	0.7738	pathogenic	-0.308	Destabilizing	0.523	D	0.46	neutral	N	0.472297518	None	None	N
S/Q	0.3341	likely_benign	0.3209	benign	-0.54	Destabilizing	0.418	N	0.331	neutral	None	None	None	None	N
S/R	0.4311	ambiguous	0.3986	ambiguous	-0.458	Destabilizing	0.418	N	0.478	neutral	None	None	None	None	N
S/T	0.069	likely_benign	0.0735	benign	-0.509	Destabilizing	None	N	0.066	neutral	N	0.401443774	None	None	N
S/V	0.1157	likely_benign	0.1249	benign	-0.308	Destabilizing	0.001	N	0.219	neutral	None	None	None	None	N
S/W	0.3149	likely_benign	0.2777	benign	-0.984	Destabilizing	0.983	D	0.524	neutral	None	None	None	None	N
S/Y	0.1546	likely_benign	0.1426	benign	-0.691	Destabilizing	0.836	D	0.581	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.