TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8305	25138;25139;25140	chr2:178718093;178718092;178718091	chr2:179582820;179582819;179582818
N2AB	7988	24187;24188;24189	chr2:178718093;178718092;178718091	chr2:179582820;179582819;179582818
N2A	7061	21406;21407;21408	chr2:178718093;178718092;178718091	chr2:179582820;179582819;179582818
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: R
• RefSeq wild type transcript codon: CGA
• RefSeq wild type template codon: GCT
• Domain: Ig-68
• Domain position: 42
• Structural Position: 59
• Q(SASA): 0.5338
• 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
R/Q	rs759985618	0.091	0.948	N	0.335	0.267	0.247322355667	gnomAD-2.1.1	5.23E-05	None	None	None	None	N	None	0	2.89788E-04	None	0	5.57E-05	None	0	None	0	1.78E-05	0
R/Q	rs759985618	0.091	0.948	N	0.335	0.267	0.247322355667	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
R/Q	rs759985618	0.091	0.948	N	0.335	0.267	0.247322355667	gnomAD-4.0.0	3.34745E-05	None	None	None	None	N	None	0	2.33403E-04	None	0	2.22846E-05	None	0	0	3.05163E-05	0	4.80369E-05

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
R/A	0.8794	likely_pathogenic	0.8964	pathogenic	0.146	Stabilizing	0.342	N	0.291	neutral	None	None	None	None	N
R/C	0.6808	likely_pathogenic	0.6908	pathogenic	-0.149	Destabilizing	0.998	D	0.307	neutral	None	None	None	None	N
R/D	0.9527	likely_pathogenic	0.9622	pathogenic	-0.256	Destabilizing	0.852	D	0.387	neutral	None	None	None	None	N
R/E	0.849	likely_pathogenic	0.8582	pathogenic	-0.206	Destabilizing	0.417	N	0.275	neutral	None	None	None	None	N
R/F	0.8813	likely_pathogenic	0.9003	pathogenic	-0.162	Destabilizing	0.942	D	0.338	neutral	None	None	None	None	N
R/G	0.7932	likely_pathogenic	0.8305	pathogenic	-0.005	Destabilizing	0.917	D	0.361	neutral	N	0.514204425	None	None	N
R/H	0.3635	ambiguous	0.3718	ambiguous	-0.574	Destabilizing	0.981	D	0.369	neutral	None	None	None	None	N
R/I	0.7133	likely_pathogenic	0.7548	pathogenic	0.498	Stabilizing	0.031	N	0.246	neutral	None	None	None	None	N
R/K	0.3737	ambiguous	0.3298	benign	-0.03	Destabilizing	0.004	N	0.173	neutral	None	None	None	None	N
R/L	0.6481	likely_pathogenic	0.7016	pathogenic	0.498	Stabilizing	0.487	N	0.329	neutral	N	0.506662377	None	None	N
R/M	0.8092	likely_pathogenic	0.8154	pathogenic	-0.018	Destabilizing	0.945	D	0.354	neutral	None	None	None	None	N
R/N	0.933	likely_pathogenic	0.9452	pathogenic	0.042	Stabilizing	0.852	D	0.27	neutral	None	None	None	None	N
R/P	0.8188	likely_pathogenic	0.8773	pathogenic	0.399	Stabilizing	0.987	D	0.348	neutral	N	0.464469038	None	None	N
R/Q	0.3994	ambiguous	0.383	ambiguous	0.025	Stabilizing	0.948	D	0.335	neutral	N	0.494405156	None	None	N
R/S	0.9143	likely_pathogenic	0.9274	pathogenic	-0.112	Destabilizing	0.184	N	0.185	neutral	None	None	None	None	N
R/T	0.8308	likely_pathogenic	0.8419	pathogenic	0.05	Stabilizing	0.544	D	0.349	neutral	None	None	None	None	N
R/V	0.7952	likely_pathogenic	0.8286	pathogenic	0.399	Stabilizing	0.023	N	0.229	neutral	None	None	None	None	N
R/W	0.49	ambiguous	0.4954	ambiguous	-0.363	Destabilizing	0.999	D	0.335	neutral	None	None	None	None	N
R/Y	0.76	likely_pathogenic	0.7823	pathogenic	0.059	Stabilizing	0.98	D	0.325	neutral	None	None	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.