TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15322	46189;46190;46191	chr2:178620557;178620556;178620555	chr2:179485284;179485283;179485282
N2AB	13681	41266;41267;41268	chr2:178620557;178620556;178620555	chr2:179485284;179485283;179485282
N2A	12754	38485;38486;38487	chr2:178620557;178620556;178620555	chr2:179485284;179485283;179485282
N2B	6257	18994;18995;18996	chr2:178620557;178620556;178620555	chr2:179485284;179485283;179485282
Novex-1	6382	19369;19370;19371	chr2:178620557;178620556;178620555	chr2:179485284;179485283;179485282
Novex-2	6449	19570;19571;19572	chr2:178620557;178620556;178620555	chr2:179485284;179485283;179485282
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: W
• RefSeq wild type transcript codon: TGG
• RefSeq wild type template codon: ACC
• Domain: Ig-105
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.391
• 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
W/C	rs2058105154	None	0.006	N	0.418	0.33	0.473458370588	gnomAD-4.0.0	6.85008E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00121E-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
W/A	0.2116	likely_benign	0.227	benign	-3.175	Highly Destabilizing	0.176	N	0.421	neutral	None	None	None	None	N
W/C	0.3894	ambiguous	0.4104	ambiguous	-1.401	Destabilizing	0.006	N	0.418	neutral	N	0.442521436	None	None	N
W/D	0.5771	likely_pathogenic	0.5573	ambiguous	-2.161	Highly Destabilizing	0.704	D	0.485	neutral	None	None	None	None	N
W/E	0.4804	ambiguous	0.4674	ambiguous	-2.105	Highly Destabilizing	0.704	D	0.487	neutral	None	None	None	None	N
W/F	0.1629	likely_benign	0.1886	benign	-2.152	Highly Destabilizing	0.936	D	0.466	neutral	None	None	None	None	N
W/G	0.1876	likely_benign	0.1721	benign	-3.362	Highly Destabilizing	0.425	N	0.451	neutral	N	0.483618818	None	None	N
W/H	0.335	likely_benign	0.3774	ambiguous	-1.877	Destabilizing	0.981	D	0.49	neutral	None	None	None	None	N
W/I	0.2766	likely_benign	0.273	benign	-2.481	Highly Destabilizing	0.704	D	0.519	neutral	None	None	None	None	N
W/K	0.6438	likely_pathogenic	0.5683	pathogenic	-1.924	Destabilizing	0.704	D	0.493	neutral	None	None	None	None	N
W/L	0.2102	likely_benign	0.1935	benign	-2.481	Highly Destabilizing	0.27	N	0.451	neutral	N	0.441740795	None	None	N
W/M	0.3702	ambiguous	0.3703	ambiguous	-1.814	Destabilizing	0.981	D	0.478	neutral	None	None	None	None	N
W/N	0.4278	ambiguous	0.4418	ambiguous	-2.22	Highly Destabilizing	0.704	D	0.505	neutral	None	None	None	None	N
W/P	0.9171	likely_pathogenic	0.8856	pathogenic	-2.731	Highly Destabilizing	0.944	D	0.545	neutral	None	None	None	None	N
W/Q	0.4663	ambiguous	0.4456	ambiguous	-2.23	Highly Destabilizing	0.944	D	0.547	neutral	None	None	None	None	N
W/R	0.5485	ambiguous	0.4687	ambiguous	-1.357	Destabilizing	0.927	D	0.547	neutral	N	0.441132102	None	None	N
W/S	0.108	likely_benign	0.1208	benign	-2.537	Highly Destabilizing	0.029	N	0.477	neutral	N	0.39556805	None	None	N
W/T	0.1387	likely_benign	0.156	benign	-2.435	Highly Destabilizing	0.013	N	0.413	neutral	None	None	None	None	N
W/V	0.2287	likely_benign	0.2375	benign	-2.731	Highly Destabilizing	0.704	D	0.481	neutral	None	None	None	None	N
W/Y	0.2819	likely_benign	0.2931	benign	-2.109	Highly Destabilizing	0.936	D	0.451	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.