TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3353	10282;10283;10284	chr2:178764234;178764233;178764232	chr2:179628961;179628960;179628959
N2AB	3353	10282;10283;10284	chr2:178764234;178764233;178764232	chr2:179628961;179628960;179628959
N2A	3353	10282;10283;10284	chr2:178764234;178764233;178764232	chr2:179628961;179628960;179628959
N2B	3307	10144;10145;10146	chr2:178764234;178764233;178764232	chr2:179628961;179628960;179628959
Novex-1	3307	10144;10145;10146	chr2:178764234;178764233;178764232	chr2:179628961;179628960;179628959
Novex-2	3307	10144;10145;10146	chr2:178764234;178764233;178764232	chr2:179628961;179628960;179628959
Novex-3	3353	10282;10283;10284	chr2:178764234;178764233;178764232	chr2:179628961;179628960;179628959

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-24
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.5977
• 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/N	None	None	0.576	N	0.262	0.248	0.258779203287	gnomAD-4.0.0	1.5906E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85673E-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
D/A	0.4218	ambiguous	0.372	ambiguous	-0.249	Destabilizing	0.956	D	0.489	neutral	D	0.552951801	None	None	N
D/C	0.9136	likely_pathogenic	0.8591	pathogenic	0.121	Stabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
D/E	0.3645	ambiguous	0.3831	ambiguous	-0.299	Destabilizing	0.978	D	0.43	neutral	D	0.571772831	None	None	N
D/F	0.9297	likely_pathogenic	0.9127	pathogenic	-0.248	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	N
D/G	0.3083	likely_benign	0.2663	benign	-0.453	Destabilizing	0.978	D	0.497	neutral	D	0.625278243	None	None	N
D/H	0.5443	ambiguous	0.4573	ambiguous	-0.186	Destabilizing	0.999	D	0.645	neutral	D	0.588754648	None	None	N
D/I	0.8562	likely_pathogenic	0.8235	pathogenic	0.24	Stabilizing	0.998	D	0.709	prob.delet.	None	None	None	None	N
D/K	0.6866	likely_pathogenic	0.6925	pathogenic	0.304	Stabilizing	0.995	D	0.612	neutral	None	None	None	None	N
D/L	0.8237	likely_pathogenic	0.8079	pathogenic	0.24	Stabilizing	0.998	D	0.684	prob.neutral	None	None	None	None	N
D/M	0.9214	likely_pathogenic	0.9071	pathogenic	0.422	Stabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
D/N	0.1259	likely_benign	0.1109	benign	0.071	Stabilizing	0.576	D	0.262	neutral	N	0.502596257	None	None	N
D/P	0.665	likely_pathogenic	0.6443	pathogenic	0.1	Stabilizing	0.998	D	0.682	prob.neutral	None	None	None	None	N
D/Q	0.6763	likely_pathogenic	0.6654	pathogenic	0.1	Stabilizing	0.998	D	0.605	neutral	None	None	None	None	N
D/R	0.7494	likely_pathogenic	0.7353	pathogenic	0.424	Stabilizing	0.998	D	0.678	prob.neutral	None	None	None	None	N
D/S	0.2503	likely_benign	0.1973	benign	-0.055	Destabilizing	0.84	D	0.253	neutral	None	None	None	None	N
D/T	0.6072	likely_pathogenic	0.5441	ambiguous	0.101	Stabilizing	0.967	D	0.601	neutral	None	None	None	None	N
D/V	0.6764	likely_pathogenic	0.6358	pathogenic	0.1	Stabilizing	0.997	D	0.702	prob.neutral	D	0.636831928	None	None	N
D/W	0.981	likely_pathogenic	0.9754	pathogenic	-0.143	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	N
D/Y	0.5666	likely_pathogenic	0.5266	ambiguous	-0.015	Destabilizing	1.0	D	0.686	prob.neutral	D	0.65709196	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.