TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18594	56005;56006;56007	chr2:178601124;178601123;178601122	chr2:179465851;179465850;179465849
N2AB	16953	51082;51083;51084	chr2:178601124;178601123;178601122	chr2:179465851;179465850;179465849
N2A	16026	48301;48302;48303	chr2:178601124;178601123;178601122	chr2:179465851;179465850;179465849
N2B	9529	28810;28811;28812	chr2:178601124;178601123;178601122	chr2:179465851;179465850;179465849
Novex-1	9654	29185;29186;29187	chr2:178601124;178601123;178601122	chr2:179465851;179465850;179465849
Novex-2	9721	29386;29387;29388	chr2:178601124;178601123;178601122	chr2:179465851;179465850;179465849
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-23
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.284
• 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
N/H	None	None	0.928	N	0.397	0.269	0.146414634003	gnomAD-4.0.0	1.70542E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.01998E-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
N/A	0.4043	ambiguous	0.3687	ambiguous	-0.726	Destabilizing	0.547	D	0.514	neutral	None	None	None	None	N
N/C	0.4994	ambiguous	0.4564	ambiguous	0.028	Stabilizing	0.985	D	0.673	neutral	None	None	None	None	N
N/D	0.1308	likely_benign	0.1275	benign	-0.938	Destabilizing	0.006	N	0.285	neutral	N	0.445157266	None	None	N
N/E	0.4	ambiguous	0.394	ambiguous	-0.876	Destabilizing	0.547	D	0.429	neutral	None	None	None	None	N
N/F	0.7704	likely_pathogenic	0.7174	pathogenic	-0.61	Destabilizing	0.945	D	0.669	neutral	None	None	None	None	N
N/G	0.3389	likely_benign	0.2707	benign	-1.032	Destabilizing	0.547	D	0.421	neutral	None	None	None	None	N
N/H	0.1636	likely_benign	0.1452	benign	-0.874	Destabilizing	0.928	D	0.397	neutral	N	0.514134562	None	None	N
N/I	0.6794	likely_pathogenic	0.6531	pathogenic	0.036	Stabilizing	0.864	D	0.663	neutral	N	0.49884479	None	None	N
N/K	0.3204	likely_benign	0.3192	benign	-0.335	Destabilizing	0.477	N	0.461	neutral	N	0.509843463	None	None	N
N/L	0.5746	likely_pathogenic	0.5528	ambiguous	0.036	Stabilizing	0.894	D	0.607	neutral	None	None	None	None	N
N/M	0.5562	ambiguous	0.5259	ambiguous	0.595	Stabilizing	0.995	D	0.588	neutral	None	None	None	None	N
N/P	0.9512	likely_pathogenic	0.9377	pathogenic	-0.189	Destabilizing	0.894	D	0.6	neutral	None	None	None	None	N
N/Q	0.373	ambiguous	0.3545	ambiguous	-1.043	Destabilizing	0.894	D	0.429	neutral	None	None	None	None	N
N/R	0.3916	ambiguous	0.3791	ambiguous	-0.249	Destabilizing	0.894	D	0.432	neutral	None	None	None	None	N
N/S	0.1269	likely_benign	0.1223	benign	-0.858	Destabilizing	0.006	N	0.281	neutral	N	0.44788814	None	None	N
N/T	0.1869	likely_benign	0.1884	benign	-0.628	Destabilizing	0.477	N	0.431	neutral	N	0.46119858	None	None	N
N/V	0.6225	likely_pathogenic	0.5984	pathogenic	-0.189	Destabilizing	0.894	D	0.657	neutral	None	None	None	None	N
N/W	0.8705	likely_pathogenic	0.8329	pathogenic	-0.411	Destabilizing	0.995	D	0.65	neutral	None	None	None	None	N
N/Y	0.2676	likely_benign	0.2379	benign	-0.189	Destabilizing	0.928	D	0.607	neutral	N	0.49209684	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.