TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34407	103444;103445;103446	chr2:178533396;178533395;178533394	chr2:179398123;179398122;179398121
N2AB	32766	98521;98522;98523	chr2:178533396;178533395;178533394	chr2:179398123;179398122;179398121
N2A	31839	95740;95741;95742	chr2:178533396;178533395;178533394	chr2:179398123;179398122;179398121
N2B	25342	76249;76250;76251	chr2:178533396;178533395;178533394	chr2:179398123;179398122;179398121
Novex-1	25467	76624;76625;76626	chr2:178533396;178533395;178533394	chr2:179398123;179398122;179398121
Novex-2	25534	76825;76826;76827	chr2:178533396;178533395;178533394	chr2:179398123;179398122;179398121
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-162
• Domain position: 45
• Structural Position: 102
• Q(SASA): 0.8917
• Predicted PPI site: I

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/A	None	None	0.003	N	0.226	0.171	0.19670166235	gnomAD-4.0.0	6.84296E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99416E-07	0	0
P/S	rs1438404457	0.108	0.338	N	0.314	0.154	0.210429274316	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	6.48E-05	0	None	0	0	None	0	None	0	0	0
P/S	rs1438404457	0.108	0.338	N	0.314	0.154	0.210429274316	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
P/S	rs1438404457	0.108	0.338	N	0.314	0.154	0.210429274316	gnomAD-4.0.0	1.85928E-06	None	None	None	None	I	None	2.66987E-05	0	None	0	0	None	0	0	8.47554E-07	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
P/A	0.1048	likely_benign	0.0999	benign	-0.298	Destabilizing	0.003	N	0.226	neutral	N	0.512777486	None	None	I
P/C	0.5565	ambiguous	0.4857	ambiguous	-0.681	Destabilizing	0.973	D	0.482	neutral	None	None	None	None	I
P/D	0.3347	likely_benign	0.3438	ambiguous	-0.311	Destabilizing	0.826	D	0.309	neutral	None	None	None	None	I
P/E	0.2197	likely_benign	0.2297	benign	-0.428	Destabilizing	0.575	D	0.337	neutral	None	None	None	None	I
P/F	0.6575	likely_pathogenic	0.5911	pathogenic	-0.641	Destabilizing	0.906	D	0.452	neutral	None	None	None	None	I
P/G	0.3461	ambiguous	0.307	benign	-0.375	Destabilizing	0.404	N	0.347	neutral	None	None	None	None	I
P/H	0.1866	likely_benign	0.1706	benign	0.038	Stabilizing	0.003	N	0.265	neutral	N	0.498290823	None	None	I
P/I	0.4532	ambiguous	0.3881	ambiguous	-0.241	Destabilizing	0.704	D	0.441	neutral	None	None	None	None	I
P/K	0.2243	likely_benign	0.2297	benign	-0.36	Destabilizing	0.575	D	0.345	neutral	None	None	None	None	I
P/L	0.1931	likely_benign	0.1752	benign	-0.241	Destabilizing	0.338	N	0.395	neutral	N	0.486515704	None	None	I
P/M	0.4063	ambiguous	0.3442	ambiguous	-0.485	Destabilizing	0.973	D	0.417	neutral	None	None	None	None	I
P/N	0.2955	likely_benign	0.2497	benign	-0.123	Destabilizing	0.826	D	0.365	neutral	None	None	None	None	I
P/Q	0.1436	likely_benign	0.136	benign	-0.346	Destabilizing	0.906	D	0.323	neutral	None	None	None	None	I
P/R	0.1583	likely_benign	0.1653	benign	0.106	Stabilizing	0.782	D	0.399	neutral	N	0.500040262	None	None	I
P/S	0.1335	likely_benign	0.1206	benign	-0.431	Destabilizing	0.338	N	0.314	neutral	N	0.483532014	None	None	I
P/T	0.1224	likely_benign	0.1024	benign	-0.456	Destabilizing	0.007	N	0.228	neutral	N	0.52020489	None	None	I
P/V	0.3123	likely_benign	0.28	benign	-0.23	Destabilizing	0.404	N	0.361	neutral	None	None	None	None	I
P/W	0.6965	likely_pathogenic	0.6698	pathogenic	-0.712	Destabilizing	0.991	D	0.57	neutral	None	None	None	None	I
P/Y	0.5288	ambiguous	0.4807	ambiguous	-0.425	Destabilizing	0.826	D	0.441	neutral	None	None	None	None	I

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.