TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32565	97918;97919;97920	chr2:178541384;178541383;178541382	chr2:179406111;179406110;179406109
N2AB	30924	92995;92996;92997	chr2:178541384;178541383;178541382	chr2:179406111;179406110;179406109
N2A	29997	90214;90215;90216	chr2:178541384;178541383;178541382	chr2:179406111;179406110;179406109
N2B	23500	70723;70724;70725	chr2:178541384;178541383;178541382	chr2:179406111;179406110;179406109
Novex-1	23625	71098;71099;71100	chr2:178541384;178541383;178541382	chr2:179406111;179406110;179406109
Novex-2	23692	71299;71300;71301	chr2:178541384;178541383;178541382	chr2:179406111;179406110;179406109
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-125
• Domain position: 67
• Structural Position: 98
• Q(SASA): 0.5341
• 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
T/A	rs1232892938	-1.11	0.002	N	0.19	0.098	0.162503812791	gnomAD-2.1.1	4.1E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.37E-05	None	0	0	0
T/A	rs1232892938	-1.11	0.002	N	0.19	0.098	0.162503812791	gnomAD-4.0.0	6.39939E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	5.80333E-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
T/A	0.0923	likely_benign	0.0921	benign	-0.752	Destabilizing	0.002	N	0.19	neutral	N	0.479000481	None	None	N
T/C	0.3453	ambiguous	0.3603	ambiguous	-0.478	Destabilizing	0.628	D	0.33	neutral	None	None	None	None	N
T/D	0.425	ambiguous	0.5009	ambiguous	0.356	Stabilizing	0.136	N	0.313	neutral	None	None	None	None	N
T/E	0.2476	likely_benign	0.276	benign	0.344	Stabilizing	0.136	N	0.292	neutral	None	None	None	None	N
T/F	0.1427	likely_benign	0.1808	benign	-1.022	Destabilizing	0.072	N	0.391	neutral	None	None	None	None	N
T/G	0.2825	likely_benign	0.3123	benign	-0.962	Destabilizing	0.136	N	0.341	neutral	None	None	None	None	N
T/H	0.2421	likely_benign	0.2833	benign	-1.065	Destabilizing	0.628	D	0.374	neutral	None	None	None	None	N
T/I	0.0492	likely_benign	0.0485	benign	-0.298	Destabilizing	None	N	0.092	neutral	N	0.431209321	None	None	N
T/K	0.2029	likely_benign	0.2384	benign	-0.405	Destabilizing	0.136	N	0.311	neutral	None	None	None	None	N
T/L	0.0508	likely_benign	0.0555	benign	-0.298	Destabilizing	0.001	N	0.128	neutral	None	None	None	None	N
T/M	0.0571	likely_benign	0.0607	benign	-0.217	Destabilizing	0.214	N	0.39	neutral	None	None	None	None	N
T/N	0.1365	likely_benign	0.1592	benign	-0.365	Destabilizing	0.266	N	0.234	neutral	N	0.483656939	None	None	N
T/P	0.2756	likely_benign	0.3325	benign	-0.418	Destabilizing	0.266	N	0.374	neutral	N	0.471959865	None	None	N
T/Q	0.1967	likely_benign	0.2123	benign	-0.477	Destabilizing	0.628	D	0.385	neutral	None	None	None	None	N
T/R	0.1564	likely_benign	0.2027	benign	-0.164	Destabilizing	0.136	N	0.367	neutral	None	None	None	None	N
T/S	0.1313	likely_benign	0.1437	benign	-0.696	Destabilizing	0.047	N	0.169	neutral	N	0.465532538	None	None	N
T/V	0.0557	likely_benign	0.0555	benign	-0.418	Destabilizing	None	N	0.098	neutral	None	None	None	None	N
T/W	0.4279	ambiguous	0.5205	ambiguous	-0.971	Destabilizing	0.864	D	0.365	neutral	None	None	None	None	N
T/Y	0.2388	likely_benign	0.2791	benign	-0.705	Destabilizing	0.136	N	0.403	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.