TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5488	16687;16688;16689	chr2:178732599;178732598;178732597	chr2:179597326;179597325;179597324
N2AB	5171	15736;15737;15738	chr2:178732599;178732598;178732597	chr2:179597326;179597325;179597324
N2A	4244	12955;12956;12957	chr2:178732599;178732598;178732597	chr2:179597326;179597325;179597324
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: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-38
• Domain position: 39
• Structural Position: 55
• Q(SASA): 0.7197
• 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/E	None	None	None	N	0.229	0.209	0.319402600006	gnomAD-4.0.0	3.18307E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71713E-06	0	0
K/N	rs760521859	0.227	None	N	0.253	0.125	0.1749357433	gnomAD-2.1.1	5.24E-05	None	None	None	None	N	None	0	3.48331E-04	None	0	0	None	0	None	0	0	1.66223E-04
K/N	rs760521859	0.227	None	N	0.253	0.125	0.1749357433	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	1.96464E-04	0	0	0	None	0	0	0	0	0
K/N	rs760521859	0.227	None	N	0.253	0.125	0.1749357433	gnomAD-4.0.0	1.17751E-05	None	None	None	None	N	None	0	3.0014E-04	None	0	0	None	0	0	0	0	1.60128E-05
K/R	None	None	None	N	0.225	0.099	0.308278614506	gnomAD-4.0.0	1.59155E-06	None	None	None	None	N	None	0	0	None	0	2.77685E-05	None	0	0	0	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	0.1696	likely_benign	0.2204	benign	-0.085	Destabilizing	None	N	0.177	neutral	None	None	None	None	N
K/C	0.5694	likely_pathogenic	0.6597	pathogenic	-0.352	Destabilizing	0.676	D	0.252	neutral	None	None	None	None	N
K/D	0.2214	likely_benign	0.3061	benign	0.111	Stabilizing	0.016	N	0.363	neutral	None	None	None	None	N
K/E	0.0692	likely_benign	0.0847	benign	0.162	Stabilizing	None	N	0.229	neutral	N	0.475203319	None	None	N
K/F	0.5913	likely_pathogenic	0.7152	pathogenic	-0.076	Destabilizing	0.356	N	0.275	neutral	None	None	None	None	N
K/G	0.2596	likely_benign	0.3621	ambiguous	-0.344	Destabilizing	0.016	N	0.365	neutral	None	None	None	None	N
K/H	0.211	likely_benign	0.2516	benign	-0.538	Destabilizing	0.214	N	0.308	neutral	None	None	None	None	N
K/I	0.2085	likely_benign	0.257	benign	0.537	Stabilizing	0.171	N	0.322	neutral	N	0.481670719	None	None	N
K/L	0.225	likely_benign	0.2991	benign	0.537	Stabilizing	0.038	N	0.359	neutral	None	None	None	None	N
K/M	0.1466	likely_benign	0.1824	benign	0.15	Stabilizing	0.628	D	0.31	neutral	None	None	None	None	N
K/N	0.188	likely_benign	0.2337	benign	-0.04	Destabilizing	None	N	0.253	neutral	N	0.485729744	None	None	N
K/P	0.7636	likely_pathogenic	0.8729	pathogenic	0.359	Stabilizing	0.136	N	0.368	neutral	None	None	None	None	N
K/Q	0.0822	likely_benign	0.091	benign	-0.116	Destabilizing	0.029	N	0.325	neutral	N	0.46829599	None	None	N
K/R	0.075	likely_benign	0.0787	benign	-0.19	Destabilizing	None	N	0.225	neutral	N	0.426662798	None	None	N
K/S	0.1877	likely_benign	0.2529	benign	-0.544	Destabilizing	None	N	0.191	neutral	None	None	None	None	N
K/T	0.0904	likely_benign	0.1051	benign	-0.322	Destabilizing	0.001	N	0.251	neutral	N	0.458889859	None	None	N
K/V	0.1708	likely_benign	0.2133	benign	0.359	Stabilizing	0.038	N	0.375	neutral	None	None	None	None	N
K/W	0.5954	likely_pathogenic	0.7065	pathogenic	-0.084	Destabilizing	0.864	D	0.27	neutral	None	None	None	None	N
K/Y	0.4389	ambiguous	0.5485	ambiguous	0.244	Stabilizing	0.356	N	0.284	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.