TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14274	43045;43046;43047	chr2:178633539;178633538;178633537	chr2:179498266;179498265;179498264
N2AB	12633	38122;38123;38124	chr2:178633539;178633538;178633537	chr2:179498266;179498265;179498264
N2A	11706	35341;35342;35343	chr2:178633539;178633538;178633537	chr2:179498266;179498265;179498264
N2B	5209	15850;15851;15852	chr2:178633539;178633538;178633537	chr2:179498266;179498265;179498264
Novex-1	5334	16225;16226;16227	chr2:178633539;178633538;178633537	chr2:179498266;179498265;179498264
Novex-2	5401	16426;16427;16428	chr2:178633539;178633538;178633537	chr2:179498266;179498265;179498264
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-93
• Domain position: 44
• Structural Position: 115
• Q(SASA): 0.2309
• 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
K/N	rs2060064294	None	0.001	N	0.129	0.033	0.0401082797425	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/N	rs2060064294	None	0.001	N	0.129	0.033	0.0401082797425	gnomAD-4.0.0	6.57384E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.4708E-05	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
K/A	0.4269	ambiguous	0.3009	benign	-0.71	Destabilizing	0.061	N	0.251	neutral	None	None	None	None	N
K/C	0.8026	likely_pathogenic	0.7188	pathogenic	-0.618	Destabilizing	0.983	D	0.387	neutral	None	None	None	None	N
K/D	0.702	likely_pathogenic	0.552	ambiguous	-0.018	Destabilizing	0.129	N	0.299	neutral	None	None	None	None	N
K/E	0.347	ambiguous	0.2199	benign	0.13	Stabilizing	0.183	N	0.207	neutral	N	0.511291049	None	None	N
K/F	0.8223	likely_pathogenic	0.7335	pathogenic	-0.302	Destabilizing	0.716	D	0.473	neutral	None	None	None	None	N
K/G	0.5903	likely_pathogenic	0.4287	ambiguous	-1.103	Destabilizing	0.129	N	0.251	neutral	None	None	None	None	N
K/H	0.3952	ambiguous	0.3321	benign	-1.379	Destabilizing	0.836	D	0.342	neutral	None	None	None	None	N
K/I	0.4086	ambiguous	0.3035	benign	0.327	Stabilizing	0.213	N	0.409	neutral	D	0.533071124	None	None	N
K/L	0.4038	ambiguous	0.3214	benign	0.327	Stabilizing	0.061	N	0.241	neutral	None	None	None	None	N
K/M	0.3425	ambiguous	0.2515	benign	0.132	Stabilizing	0.027	N	0.221	neutral	None	None	None	None	N
K/N	0.5391	ambiguous	0.4033	ambiguous	-0.564	Destabilizing	0.001	N	0.129	neutral	N	0.446653015	None	None	N
K/P	0.8748	likely_pathogenic	0.8057	pathogenic	0.011	Stabilizing	0.593	D	0.417	neutral	None	None	None	None	N
K/Q	0.216	likely_benign	0.1607	benign	-0.519	Destabilizing	0.351	N	0.211	neutral	D	0.533071124	None	None	N
K/R	0.0906	likely_benign	0.0807	benign	-0.639	Destabilizing	0.001	N	0.121	neutral	N	0.419259115	None	None	N
K/S	0.5377	ambiguous	0.4025	ambiguous	-1.243	Destabilizing	0.129	N	0.155	neutral	None	None	None	None	N
K/T	0.2379	likely_benign	0.1712	benign	-0.869	Destabilizing	0.003	N	0.165	neutral	N	0.449318152	None	None	N
K/V	0.3944	ambiguous	0.2949	benign	0.011	Stabilizing	0.129	N	0.28	neutral	None	None	None	None	N
K/W	0.829	likely_pathogenic	0.7802	pathogenic	-0.197	Destabilizing	0.983	D	0.382	neutral	None	None	None	None	N
K/Y	0.7016	likely_pathogenic	0.5965	pathogenic	0.086	Stabilizing	0.94	D	0.421	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.