TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27287	82084;82085;82086	chr2:178564273;178564272;178564271	chr2:179429000;179428999;179428998
N2AB	25646	77161;77162;77163	chr2:178564273;178564272;178564271	chr2:179429000;179428999;179428998
N2A	24719	74380;74381;74382	chr2:178564273;178564272;178564271	chr2:179429000;179428999;179428998
N2B	18222	54889;54890;54891	chr2:178564273;178564272;178564271	chr2:179429000;179428999;179428998
Novex-1	18347	55264;55265;55266	chr2:178564273;178564272;178564271	chr2:179429000;179428999;179428998
Novex-2	18414	55465;55466;55467	chr2:178564273;178564272;178564271	chr2:179429000;179428999;179428998
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-140
• Domain position: 10
• Structural Position: 16
• Q(SASA): 0.1466
• 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
V/I	rs1704823668	None	0.997	N	0.505	0.466	0.846003560123	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
V/I	rs1704823668	None	0.997	N	0.505	0.466	0.846003560123	gnomAD-4.0.0	1.85963E-06	None	None	None	None	N	None	4.00502E-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
V/A	0.4126	ambiguous	0.3337	benign	-1.984	Destabilizing	0.999	D	0.538	neutral	N	0.487066044	None	None	N
V/C	0.7742	likely_pathogenic	0.726	pathogenic	-1.301	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
V/D	0.924	likely_pathogenic	0.9167	pathogenic	-2.528	Highly Destabilizing	1.0	D	0.811	deleterious	D	0.564401497	None	None	N
V/E	0.8198	likely_pathogenic	0.8017	pathogenic	-2.376	Highly Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
V/F	0.3248	likely_benign	0.2861	benign	-1.267	Destabilizing	1.0	D	0.811	deleterious	D	0.537307566	None	None	N
V/G	0.5602	ambiguous	0.511	ambiguous	-2.457	Highly Destabilizing	1.0	D	0.785	deleterious	D	0.552538212	None	None	N
V/H	0.8813	likely_pathogenic	0.8559	pathogenic	-2.247	Highly Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
V/I	0.0781	likely_benign	0.0785	benign	-0.694	Destabilizing	0.997	D	0.505	neutral	N	0.503132837	None	None	N
V/K	0.7174	likely_pathogenic	0.6926	pathogenic	-1.798	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
V/L	0.22	likely_benign	0.2137	benign	-0.694	Destabilizing	0.997	D	0.546	neutral	N	0.516668416	None	None	N
V/M	0.2466	likely_benign	0.2199	benign	-0.505	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
V/N	0.8041	likely_pathogenic	0.778	pathogenic	-1.889	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
V/P	0.9683	likely_pathogenic	0.9638	pathogenic	-1.095	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
V/Q	0.7336	likely_pathogenic	0.6978	pathogenic	-1.843	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
V/R	0.6517	likely_pathogenic	0.6259	pathogenic	-1.467	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
V/S	0.6201	likely_pathogenic	0.5577	ambiguous	-2.434	Highly Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
V/T	0.4099	ambiguous	0.3724	ambiguous	-2.16	Highly Destabilizing	0.999	D	0.602	neutral	None	None	None	None	N
V/W	0.9395	likely_pathogenic	0.9235	pathogenic	-1.788	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
V/Y	0.7954	likely_pathogenic	0.7689	pathogenic	-1.416	Destabilizing	1.0	D	0.812	deleterious	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.