TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18424	55495;55496;55497	chr2:178601914;178601913;178601912	chr2:179466641;179466640;179466639
N2AB	16783	50572;50573;50574	chr2:178601914;178601913;178601912	chr2:179466641;179466640;179466639
N2A	15856	47791;47792;47793	chr2:178601914;178601913;178601912	chr2:179466641;179466640;179466639
N2B	9359	28300;28301;28302	chr2:178601914;178601913;178601912	chr2:179466641;179466640;179466639
Novex-1	9484	28675;28676;28677	chr2:178601914;178601913;178601912	chr2:179466641;179466640;179466639
Novex-2	9551	28876;28877;28878	chr2:178601914;178601913;178601912	chr2:179466641;179466640;179466639
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-115
• Domain position: 43
• Structural Position: 63
• Q(SASA): 0.8184
• 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/G	rs1553674352	None	0.324	N	0.319	0.144	0.117506650769	gnomAD-4.0.0	4.78258E-06	None	None	None	None	N	None	0	0	None	0	2.78956E-05	None	0	0	5.72531E-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	0.1273	likely_benign	0.1346	benign	-0.116	Destabilizing	0.09	N	0.343	neutral	N	0.494649432	None	None	N
D/C	0.4289	ambiguous	0.4352	ambiguous	-0.128	Destabilizing	0.981	D	0.369	neutral	None	None	None	None	N
D/E	0.1032	likely_benign	0.1157	benign	-0.182	Destabilizing	0.001	N	0.205	neutral	N	0.419863672	None	None	N
D/F	0.4571	ambiguous	0.4582	ambiguous	-0.06	Destabilizing	0.818	D	0.36	neutral	None	None	None	None	N
D/G	0.0875	likely_benign	0.0878	benign	-0.288	Destabilizing	0.324	N	0.319	neutral	N	0.494129357	None	None	N
D/H	0.2346	likely_benign	0.228	benign	0.368	Stabilizing	0.928	D	0.311	neutral	N	0.494476074	None	None	N
D/I	0.325	likely_benign	0.3463	ambiguous	0.284	Stabilizing	0.008	N	0.329	neutral	None	None	None	None	N
D/K	0.2478	likely_benign	0.2624	benign	0.262	Stabilizing	0.241	N	0.353	neutral	None	None	None	None	N
D/L	0.2937	likely_benign	0.3172	benign	0.284	Stabilizing	0.116	N	0.364	neutral	None	None	None	None	N
D/M	0.4543	ambiguous	0.4532	ambiguous	0.171	Stabilizing	0.818	D	0.352	neutral	None	None	None	None	N
D/N	0.0831	likely_benign	0.0778	benign	0.038	Stabilizing	0.324	N	0.36	neutral	N	0.408299884	None	None	N
D/P	0.4812	ambiguous	0.58	pathogenic	0.172	Stabilizing	0.818	D	0.323	neutral	None	None	None	None	N
D/Q	0.2289	likely_benign	0.2405	benign	0.074	Stabilizing	0.527	D	0.313	neutral	None	None	None	None	N
D/R	0.3053	likely_benign	0.3121	benign	0.547	Stabilizing	0.69	D	0.355	neutral	None	None	None	None	N
D/S	0.1105	likely_benign	0.1084	benign	-0.105	Destabilizing	0.241	N	0.34	neutral	None	None	None	None	N
D/T	0.2003	likely_benign	0.2124	benign	0.031	Stabilizing	0.388	N	0.331	neutral	None	None	None	None	N
D/V	0.1986	likely_benign	0.2097	benign	0.172	Stabilizing	0.006	N	0.332	neutral	N	0.476237029	None	None	N
D/W	0.7117	likely_pathogenic	0.7218	pathogenic	0.033	Stabilizing	0.981	D	0.482	neutral	None	None	None	None	N
D/Y	0.179	likely_benign	0.1789	benign	0.171	Stabilizing	0.912	D	0.355	neutral	N	0.494996148	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.