TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7837	23734;23735;23736	chr2:178720133;178720132;178720131	chr2:179584860;179584859;179584858
N2AB	7520	22783;22784;22785	chr2:178720133;178720132;178720131	chr2:179584860;179584859;179584858
N2A	6593	20002;20003;20004	chr2:178720133;178720132;178720131	chr2:179584860;179584859;179584858
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: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-63
• Domain position: 43
• Structural Position: 59
• Q(SASA): 0.7583
• 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
R/G	None	None	0.978	N	0.503	0.399	0.318828661733	gnomAD-4.0.0	3.18281E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85868E-06	0	3.02444E-05

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	0.5213	ambiguous	0.4753	ambiguous	0.05	Stabilizing	0.967	D	0.538	neutral	None	None	None	None	N
R/C	0.3862	ambiguous	0.3545	ambiguous	-0.363	Destabilizing	1.0	D	0.629	neutral	None	None	None	None	N
R/D	0.7743	likely_pathogenic	0.7484	pathogenic	-0.397	Destabilizing	0.935	D	0.527	neutral	None	None	None	None	N
R/E	0.3943	ambiguous	0.3614	ambiguous	-0.349	Destabilizing	0.047	N	0.28	neutral	None	None	None	None	N
R/F	0.6553	likely_pathogenic	0.6258	pathogenic	-0.266	Destabilizing	0.996	D	0.581	neutral	None	None	None	None	N
R/G	0.347	ambiguous	0.2993	benign	-0.094	Destabilizing	0.978	D	0.503	neutral	N	0.49159504	None	None	N
R/H	0.1566	likely_benign	0.1519	benign	-0.592	Destabilizing	0.996	D	0.512	neutral	None	None	None	None	N
R/I	0.4253	ambiguous	0.3926	ambiguous	0.384	Stabilizing	0.995	D	0.587	neutral	N	0.50024232	None	None	N
R/K	0.1538	likely_benign	0.1413	benign	-0.253	Destabilizing	0.518	D	0.477	neutral	N	0.481878575	None	None	N
R/L	0.3347	likely_benign	0.3173	benign	0.384	Stabilizing	0.961	D	0.481	neutral	None	None	None	None	N
R/M	0.4128	ambiguous	0.3682	ambiguous	-0.135	Destabilizing	0.999	D	0.513	neutral	None	None	None	None	N
R/N	0.7301	likely_pathogenic	0.686	pathogenic	-0.268	Destabilizing	0.983	D	0.496	neutral	None	None	None	None	N
R/P	0.652	likely_pathogenic	0.6238	pathogenic	0.291	Stabilizing	0.998	D	0.55	neutral	None	None	None	None	N
R/Q	0.123	likely_benign	0.1153	benign	-0.258	Destabilizing	0.955	D	0.531	neutral	None	None	None	None	N
R/S	0.6024	likely_pathogenic	0.5603	ambiguous	-0.394	Destabilizing	0.956	D	0.546	neutral	N	0.507083664	None	None	N
R/T	0.3078	likely_benign	0.2693	benign	-0.237	Destabilizing	0.978	D	0.499	neutral	N	0.505448868	None	None	N
R/V	0.4893	ambiguous	0.4569	ambiguous	0.291	Stabilizing	0.984	D	0.554	neutral	None	None	None	None	N
R/W	0.1934	likely_benign	0.1795	benign	-0.471	Destabilizing	1.0	D	0.645	neutral	None	None	None	None	N
R/Y	0.5227	ambiguous	0.4929	ambiguous	-0.061	Destabilizing	0.996	D	0.553	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.