TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26919	80980;80981;80982	chr2:178565377;178565376;178565375	chr2:179430104;179430103;179430102
N2AB	25278	76057;76058;76059	chr2:178565377;178565376;178565375	chr2:179430104;179430103;179430102
N2A	24351	73276;73277;73278	chr2:178565377;178565376;178565375	chr2:179430104;179430103;179430102
N2B	17854	53785;53786;53787	chr2:178565377;178565376;178565375	chr2:179430104;179430103;179430102
Novex-1	17979	54160;54161;54162	chr2:178565377;178565376;178565375	chr2:179430104;179430103;179430102
Novex-2	18046	54361;54362;54363	chr2:178565377;178565376;178565375	chr2:179430104;179430103;179430102
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-139
• Domain position: 40
• Structural Position: 56
• Q(SASA): 0.4881
• 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	rs879200886	None	0.001	N	0.179	0.136	None	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	9.66E-05	0	0	0	0	None	0	0	0	0	0
P/T	rs879200886	None	0.001	N	0.179	0.136	None	gnomAD-4.0.0	2.63103E-05	None	None	None	None	N	None	9.6623E-05	0	None	0	0	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
P/A	0.0617	likely_benign	0.0608	benign	-0.602	Destabilizing	0.003	N	0.168	neutral	N	0.486940465	None	None	N
P/C	0.3179	likely_benign	0.2873	benign	-0.643	Destabilizing	0.944	D	0.403	neutral	None	None	None	None	N
P/D	0.258	likely_benign	0.2504	benign	-0.507	Destabilizing	0.388	N	0.321	neutral	None	None	None	None	N
P/E	0.1876	likely_benign	0.1855	benign	-0.613	Destabilizing	0.388	N	0.28	neutral	None	None	None	None	N
P/F	0.2557	likely_benign	0.2234	benign	-0.754	Destabilizing	0.818	D	0.416	neutral	None	None	None	None	N
P/G	0.2107	likely_benign	0.2095	benign	-0.749	Destabilizing	0.116	N	0.315	neutral	None	None	None	None	N
P/H	0.1223	likely_benign	0.1193	benign	-0.3	Destabilizing	0.928	D	0.387	neutral	N	0.509952784	None	None	N
P/I	0.1236	likely_benign	0.1138	benign	-0.36	Destabilizing	0.527	D	0.388	neutral	None	None	None	None	N
P/K	0.1427	likely_benign	0.1527	benign	-0.618	Destabilizing	0.241	N	0.275	neutral	None	None	None	None	N
P/L	0.0677	likely_benign	0.0654	benign	-0.36	Destabilizing	0.193	N	0.355	neutral	N	0.49931233	None	None	N
P/M	0.1489	likely_benign	0.1363	benign	-0.413	Destabilizing	0.818	D	0.387	neutral	None	None	None	None	N
P/N	0.1686	likely_benign	0.1519	benign	-0.351	Destabilizing	0.241	N	0.37	neutral	None	None	None	None	N
P/Q	0.1047	likely_benign	0.1042	benign	-0.6	Destabilizing	0.69	D	0.337	neutral	None	None	None	None	N
P/R	0.1169	likely_benign	0.1234	benign	-0.059	Destabilizing	0.627	D	0.369	neutral	N	0.490176235	None	None	N
P/S	0.095	likely_benign	0.0907	benign	-0.688	Destabilizing	0.006	N	0.229	neutral	N	0.513433633	None	None	N
P/T	0.0717	likely_benign	0.0707	benign	-0.698	Destabilizing	0.001	N	0.179	neutral	N	0.52032232	None	None	N
P/V	0.0953	likely_benign	0.0919	benign	-0.406	Destabilizing	0.241	N	0.334	neutral	None	None	None	None	N
P/W	0.4438	ambiguous	0.4252	ambiguous	-0.842	Destabilizing	0.981	D	0.479	neutral	None	None	None	None	N
P/Y	0.2543	likely_benign	0.2301	benign	-0.56	Destabilizing	0.818	D	0.409	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.