TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8085	24478;24479;24480	chr2:178718947;178718946;178718945	chr2:179583674;179583673;179583672
N2AB	7768	23527;23528;23529	chr2:178718947;178718946;178718945	chr2:179583674;179583673;179583672
N2A	6841	20746;20747;20748	chr2:178718947;178718946;178718945	chr2:179583674;179583673;179583672
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: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-66
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.7247
• 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	rs1553904192	None	0.324	N	0.341	0.23	0.342865806769	gnomAD-4.0.0	1.60225E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.87573E-06	0	0
D/V	None	None	0.324	N	0.442	0.396	0.601175442443	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
D/A	0.0928	likely_benign	0.0902	benign	-0.11	Destabilizing	0.006	N	0.181	neutral	N	0.507622382	None	None	N
D/C	0.4598	ambiguous	0.473	ambiguous	0.003	Stabilizing	0.981	D	0.381	neutral	None	None	None	None	N
D/E	0.087	likely_benign	0.0917	benign	-0.223	Destabilizing	0.001	N	0.087	neutral	N	0.399454767	None	None	N
D/F	0.3707	ambiguous	0.3774	ambiguous	-0.019	Destabilizing	0.932	D	0.408	neutral	None	None	None	None	N
D/G	0.1055	likely_benign	0.102	benign	-0.282	Destabilizing	0.001	N	0.109	neutral	N	0.508315815	None	None	N
D/H	0.1591	likely_benign	0.1695	benign	0.356	Stabilizing	0.773	D	0.401	neutral	N	0.484612236	None	None	N
D/I	0.191	likely_benign	0.1948	benign	0.29	Stabilizing	0.818	D	0.432	neutral	None	None	None	None	N
D/K	0.1477	likely_benign	0.1593	benign	0.491	Stabilizing	0.241	N	0.363	neutral	None	None	None	None	N
D/L	0.2008	likely_benign	0.2073	benign	0.29	Stabilizing	0.388	N	0.441	neutral	None	None	None	None	N
D/M	0.3895	ambiguous	0.4123	ambiguous	0.252	Stabilizing	0.981	D	0.388	neutral	None	None	None	None	N
D/N	0.0805	likely_benign	0.0811	benign	0.119	Stabilizing	0.324	N	0.341	neutral	N	0.513721635	None	None	N
D/P	0.346	ambiguous	0.3634	ambiguous	0.178	Stabilizing	0.818	D	0.422	neutral	None	None	None	None	N
D/Q	0.148	likely_benign	0.1601	benign	0.163	Stabilizing	0.024	N	0.093	neutral	None	None	None	None	N
D/R	0.1776	likely_benign	0.1875	benign	0.695	Stabilizing	0.388	N	0.406	neutral	None	None	None	None	N
D/S	0.0824	likely_benign	0.0842	benign	0.039	Stabilizing	0.116	N	0.357	neutral	None	None	None	None	N
D/T	0.1414	likely_benign	0.1481	benign	0.185	Stabilizing	0.388	N	0.357	neutral	None	None	None	None	N
D/V	0.1168	likely_benign	0.1169	benign	0.178	Stabilizing	0.324	N	0.442	neutral	N	0.497098744	None	None	N
D/W	0.7426	likely_pathogenic	0.7595	pathogenic	0.101	Stabilizing	0.981	D	0.447	neutral	None	None	None	None	N
D/Y	0.1592	likely_benign	0.1606	benign	0.229	Stabilizing	0.912	D	0.422	neutral	N	0.492391507	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.