TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23577	70954;70955;70956	chr2:178575403;178575402;178575401	chr2:179440130;179440129;179440128
N2AB	21936	66031;66032;66033	chr2:178575403;178575402;178575401	chr2:179440130;179440129;179440128
N2A	21009	63250;63251;63252	chr2:178575403;178575402;178575401	chr2:179440130;179440129;179440128
N2B	14512	43759;43760;43761	chr2:178575403;178575402;178575401	chr2:179440130;179440129;179440128
Novex-1	14637	44134;44135;44136	chr2:178575403;178575402;178575401	chr2:179440130;179440129;179440128
Novex-2	14704	44335;44336;44337	chr2:178575403;178575402;178575401	chr2:179440130;179440129;179440128
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-59
• Domain position: 46
• Structural Position: 63
• Q(SASA): 0.8209
• 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	rs1343180009	0.581	0.003	N	0.314	0.118	0.258283824007	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
D/N	rs1343180009	0.581	0.003	N	0.314	0.118	0.258283824007	gnomAD-4.0.0	1.59174E-06	None	None	None	None	N	None	0	2.28666E-05	None	0	0	None	0	0	0	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	0.1262	likely_benign	0.1149	benign	0.093	Stabilizing	0.316	N	0.379	neutral	N	0.495564657	None	None	N
D/C	0.5108	ambiguous	0.477	ambiguous	-0.04	Destabilizing	0.986	D	0.445	neutral	None	None	None	None	N
D/E	0.0922	likely_benign	0.0903	benign	-0.34	Destabilizing	0.001	N	0.147	neutral	N	0.437380358	None	None	N
D/F	0.4773	ambiguous	0.4381	ambiguous	-0.109	Destabilizing	0.987	D	0.451	neutral	None	None	None	None	N
D/G	0.1274	likely_benign	0.1131	benign	0.016	Stabilizing	0.447	N	0.434	neutral	N	0.469818063	None	None	N
D/H	0.2128	likely_benign	0.1936	benign	0.464	Stabilizing	0.955	D	0.476	neutral	N	0.467988196	None	None	N
D/I	0.2488	likely_benign	0.2262	benign	0.223	Stabilizing	0.974	D	0.445	neutral	None	None	None	None	N
D/K	0.2109	likely_benign	0.2006	benign	0.469	Stabilizing	0.032	N	0.354	neutral	None	None	None	None	N
D/L	0.2271	likely_benign	0.2031	benign	0.223	Stabilizing	0.842	D	0.415	neutral	None	None	None	None	N
D/M	0.4019	ambiguous	0.3827	ambiguous	0.068	Stabilizing	0.997	D	0.45	neutral	None	None	None	None	N
D/N	0.0856	likely_benign	0.0815	benign	0.36	Stabilizing	0.003	N	0.314	neutral	N	0.486731743	None	None	N
D/P	0.3408	ambiguous	0.3184	benign	0.197	Stabilizing	0.599	D	0.455	neutral	None	None	None	None	N
D/Q	0.1982	likely_benign	0.189	benign	0.33	Stabilizing	0.799	D	0.405	neutral	None	None	None	None	N
D/R	0.2705	likely_benign	0.252	benign	0.611	Stabilizing	0.842	D	0.411	neutral	None	None	None	None	N
D/S	0.0859	likely_benign	0.0811	benign	0.248	Stabilizing	0.379	N	0.386	neutral	None	None	None	None	N
D/T	0.1311	likely_benign	0.1246	benign	0.312	Stabilizing	0.017	N	0.364	neutral	None	None	None	None	N
D/V	0.1537	likely_benign	0.1399	benign	0.197	Stabilizing	0.412	N	0.415	neutral	D	0.522769901	None	None	N
D/W	0.8031	likely_pathogenic	0.7756	pathogenic	-0.117	Destabilizing	0.999	D	0.505	neutral	None	None	None	None	N
D/Y	0.2317	likely_benign	0.2096	benign	0.105	Stabilizing	0.994	D	0.448	neutral	N	0.474722919	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.