TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32248	96967;96968;96969	chr2:178543231;178543230;178543229	chr2:179407958;179407957;179407956
N2AB	30607	92044;92045;92046	chr2:178543231;178543230;178543229	chr2:179407958;179407957;179407956
N2A	29680	89263;89264;89265	chr2:178543231;178543230;178543229	chr2:179407958;179407957;179407956
N2B	23183	69772;69773;69774	chr2:178543231;178543230;178543229	chr2:179407958;179407957;179407956
Novex-1	23308	70147;70148;70149	chr2:178543231;178543230;178543229	chr2:179407958;179407957;179407956
Novex-2	23375	70348;70349;70350	chr2:178543231;178543230;178543229	chr2:179407958;179407957;179407956
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-123
• Domain position: 47
• Structural Position: 64
• Q(SASA): 0.6677
• 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
R/S	None	None	0.896	N	0.439	0.236	0.237489013734	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
R/A	0.3904	ambiguous	0.3916	ambiguous	0.206	Stabilizing	0.919	D	0.46	neutral	None	None	None	None	I
R/C	0.235	likely_benign	0.225	benign	0.121	Stabilizing	0.999	D	0.613	neutral	None	None	None	None	I
R/D	0.5918	likely_pathogenic	0.6011	pathogenic	-0.142	Destabilizing	0.976	D	0.497	neutral	None	None	None	None	I
R/E	0.3563	ambiguous	0.3577	ambiguous	-0.086	Destabilizing	0.851	D	0.445	neutral	None	None	None	None	I
R/F	0.5618	ambiguous	0.5704	pathogenic	-0.023	Destabilizing	0.996	D	0.576	neutral	None	None	None	None	I
R/G	0.2399	likely_benign	0.2377	benign	0.03	Stabilizing	0.896	D	0.429	neutral	N	0.478979051	None	None	I
R/H	0.1068	likely_benign	0.1115	benign	-0.565	Destabilizing	0.996	D	0.444	neutral	None	None	None	None	I
R/I	0.269	likely_benign	0.2703	benign	0.63	Stabilizing	0.984	D	0.589	neutral	N	0.503589494	None	None	I
R/K	0.0915	likely_benign	0.091	benign	0.174	Stabilizing	0.011	N	0.319	neutral	N	0.43640171	None	None	I
R/L	0.249	likely_benign	0.2502	benign	0.63	Stabilizing	0.919	D	0.429	neutral	None	None	None	None	I
R/M	0.2539	likely_benign	0.2483	benign	0.141	Stabilizing	0.999	D	0.452	neutral	None	None	None	None	I
R/N	0.4518	ambiguous	0.4509	ambiguous	0.382	Stabilizing	0.976	D	0.42	neutral	None	None	None	None	I
R/P	0.7441	likely_pathogenic	0.7414	pathogenic	0.508	Stabilizing	0.988	D	0.531	neutral	None	None	None	None	I
R/Q	0.1096	likely_benign	0.1136	benign	0.316	Stabilizing	0.976	D	0.437	neutral	None	None	None	None	I
R/S	0.4547	ambiguous	0.4548	ambiguous	0.179	Stabilizing	0.896	D	0.439	neutral	N	0.467780623	None	None	I
R/T	0.2181	likely_benign	0.2198	benign	0.354	Stabilizing	0.896	D	0.421	neutral	N	0.445983985	None	None	I
R/V	0.3395	likely_benign	0.3481	ambiguous	0.508	Stabilizing	0.988	D	0.585	neutral	None	None	None	None	I
R/W	0.2309	likely_benign	0.2283	benign	-0.174	Destabilizing	0.999	D	0.641	neutral	None	None	None	None	I
R/Y	0.3744	ambiguous	0.3815	ambiguous	0.24	Stabilizing	0.996	D	0.526	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.