TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21505	64738;64739;64740	chr2:178585231;178585230;178585229	chr2:179449958;179449957;179449956
N2AB	19864	59815;59816;59817	chr2:178585231;178585230;178585229	chr2:179449958;179449957;179449956
N2A	18937	57034;57035;57036	chr2:178585231;178585230;178585229	chr2:179449958;179449957;179449956
N2B	12440	37543;37544;37545	chr2:178585231;178585230;178585229	chr2:179449958;179449957;179449956
Novex-1	12565	37918;37919;37920	chr2:178585231;178585230;178585229	chr2:179449958;179449957;179449956
Novex-2	12632	38119;38120;38121	chr2:178585231;178585230;178585229	chr2:179449958;179449957;179449956
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-124
• Domain position: 37
• Structural Position: 55
• Q(SASA): 0.5609
• 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	0.324	N	0.318	0.194	0.225215365344	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-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	0.0904	likely_benign	0.0854	benign	-0.224	Destabilizing	0.193	N	0.349	neutral	N	0.456558843	None	None	N
D/C	0.3793	ambiguous	0.3685	ambiguous	-0.006	Destabilizing	0.981	D	0.455	neutral	None	None	None	None	N
D/E	0.0705	likely_benign	0.0689	benign	-0.297	Destabilizing	None	N	0.163	neutral	N	0.416384302	None	None	N
D/F	0.3531	ambiguous	0.3593	ambiguous	-0.222	Destabilizing	0.818	D	0.425	neutral	None	None	None	None	N
D/G	0.1161	likely_benign	0.1134	benign	-0.407	Destabilizing	0.324	N	0.331	neutral	N	0.442418897	None	None	N
D/H	0.1622	likely_benign	0.1598	benign	-0.029	Destabilizing	0.003	N	0.287	neutral	N	0.485246955	None	None	N
D/I	0.1448	likely_benign	0.1415	benign	0.205	Stabilizing	0.818	D	0.429	neutral	None	None	None	None	N
D/K	0.1597	likely_benign	0.1536	benign	0.264	Stabilizing	0.241	N	0.317	neutral	None	None	None	None	N
D/L	0.1856	likely_benign	0.1828	benign	0.205	Stabilizing	0.69	D	0.414	neutral	None	None	None	None	N
D/M	0.2493	likely_benign	0.2496	benign	0.268	Stabilizing	0.944	D	0.424	neutral	None	None	None	None	N
D/N	0.0738	likely_benign	0.0746	benign	0.033	Stabilizing	0.324	N	0.318	neutral	N	0.445669846	None	None	N
D/P	0.6899	likely_pathogenic	0.6906	pathogenic	0.084	Stabilizing	0.818	D	0.327	neutral	None	None	None	None	N
D/Q	0.1375	likely_benign	0.136	benign	0.053	Stabilizing	0.008	N	0.208	neutral	None	None	None	None	N
D/R	0.2188	likely_benign	0.2183	benign	0.436	Stabilizing	0.241	N	0.421	neutral	None	None	None	None	N
D/S	0.0845	likely_benign	0.082	benign	-0.083	Destabilizing	0.241	N	0.291	neutral	None	None	None	None	N
D/T	0.1003	likely_benign	0.0949	benign	0.054	Stabilizing	0.388	N	0.36	neutral	None	None	None	None	N
D/V	0.0925	likely_benign	0.0888	benign	0.084	Stabilizing	0.627	D	0.409	neutral	N	0.412077347	None	None	N
D/W	0.6721	likely_pathogenic	0.6774	pathogenic	-0.124	Destabilizing	0.981	D	0.501	neutral	None	None	None	None	N
D/Y	0.1392	likely_benign	0.1375	benign	0.002	Stabilizing	0.627	D	0.433	neutral	N	0.511990839	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.