TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7557	22894;22895;22896	chr2:178721994;178721993;178721992	chr2:179586721;179586720;179586719
N2AB	7240	21943;21944;21945	chr2:178721994;178721993;178721992	chr2:179586721;179586720;179586719
N2A	6313	19162;19163;19164	chr2:178721994;178721993;178721992	chr2:179586721;179586720;179586719
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: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-60
• Domain position: 43
• Structural Position: 70
• Q(SASA): 0.8529
• 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
P/T	rs758231381	-0.12	0.001	N	0.145	0.179	0.313210971179	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
P/T	rs758231381	-0.12	0.001	N	0.145	0.179	0.313210971179	gnomAD-4.0.0	6.36752E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	5.73296E-05	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
P/A	0.0718	likely_benign	0.0931	benign	-0.418	Destabilizing	0.036	N	0.224	neutral	N	0.415232296	None	None	N
P/C	0.6613	likely_pathogenic	0.7614	pathogenic	-0.745	Destabilizing	0.978	D	0.344	neutral	None	None	None	None	N
P/D	0.6097	likely_pathogenic	0.7637	pathogenic	-0.331	Destabilizing	0.118	N	0.32	neutral	None	None	None	None	N
P/E	0.3663	ambiguous	0.5073	ambiguous	-0.426	Destabilizing	0.175	N	0.325	neutral	None	None	None	None	N
P/F	0.5315	ambiguous	0.6911	pathogenic	-0.607	Destabilizing	0.98	D	0.372	neutral	None	None	None	None	N
P/G	0.3179	likely_benign	0.428	ambiguous	-0.543	Destabilizing	0.36	N	0.327	neutral	None	None	None	None	N
P/H	0.2553	likely_benign	0.3663	ambiguous	-0.076	Destabilizing	0.976	D	0.34	neutral	N	0.498773612	None	None	N
P/I	0.3449	ambiguous	0.4848	ambiguous	-0.23	Destabilizing	0.871	D	0.418	neutral	None	None	None	None	N
P/K	0.3938	ambiguous	0.5498	ambiguous	-0.479	Destabilizing	0.871	D	0.325	neutral	None	None	None	None	N
P/L	0.128	likely_benign	0.1985	benign	-0.23	Destabilizing	0.719	D	0.382	neutral	N	0.474357957	None	None	N
P/M	0.2933	likely_benign	0.4034	ambiguous	-0.507	Destabilizing	0.982	D	0.341	neutral	None	None	None	None	N
P/N	0.3586	ambiguous	0.5005	ambiguous	-0.292	Destabilizing	0.457	N	0.387	neutral	None	None	None	None	N
P/Q	0.1815	likely_benign	0.2685	benign	-0.483	Destabilizing	0.947	D	0.344	neutral	None	None	None	None	N
P/R	0.2595	likely_benign	0.3901	ambiguous	-0.014	Destabilizing	0.947	D	0.402	neutral	N	0.466565193	None	None	N
P/S	0.1174	likely_benign	0.1652	benign	-0.626	Destabilizing	0.023	N	0.157	neutral	N	0.390448495	None	None	N
P/T	0.0838	likely_benign	0.1153	benign	-0.619	Destabilizing	0.001	N	0.145	neutral	N	0.429681673	None	None	N
P/V	0.227	likely_benign	0.3145	benign	-0.26	Destabilizing	0.372	N	0.359	neutral	None	None	None	None	N
P/W	0.7026	likely_pathogenic	0.8221	pathogenic	-0.698	Destabilizing	0.998	D	0.37	neutral	None	None	None	None	N
P/Y	0.5246	ambiguous	0.6745	pathogenic	-0.407	Destabilizing	0.993	D	0.365	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.