TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20364	61315;61316;61317	chr2:178590635;178590634;178590633	chr2:179455362;179455361;179455360
N2AB	18723	56392;56393;56394	chr2:178590635;178590634;178590633	chr2:179455362;179455361;179455360
N2A	17796	53611;53612;53613	chr2:178590635;178590634;178590633	chr2:179455362;179455361;179455360
N2B	11299	34120;34121;34122	chr2:178590635;178590634;178590633	chr2:179455362;179455361;179455360
Novex-1	11424	34495;34496;34497	chr2:178590635;178590634;178590633	chr2:179455362;179455361;179455360
Novex-2	11491	34696;34697;34698	chr2:178590635;178590634;178590633	chr2:179455362;179455361;179455360
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-35
• Domain position: 94
• Structural Position: 129
• Q(SASA): 0.4965
• 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
K/T	None	None	0.999	N	0.776	0.282	0.256283259241	gnomAD-4.0.0	1.59266E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86105E-06	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
K/A	0.5381	ambiguous	0.6375	pathogenic	-0.064	Destabilizing	0.998	D	0.82	deleterious	None	None	None	None	N
K/C	0.7838	likely_pathogenic	0.8401	pathogenic	-0.327	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
K/D	0.8536	likely_pathogenic	0.8869	pathogenic	0.164	Stabilizing	0.999	D	0.811	deleterious	None	None	None	None	N
K/E	0.3305	likely_benign	0.3817	ambiguous	0.207	Stabilizing	0.997	D	0.83	deleterious	N	0.500919256	None	None	N
K/F	0.8343	likely_pathogenic	0.8778	pathogenic	-0.081	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
K/G	0.7692	likely_pathogenic	0.8408	pathogenic	-0.319	Destabilizing	0.999	D	0.703	prob.delet.	None	None	None	None	N
K/H	0.4219	ambiguous	0.4835	ambiguous	-0.56	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
K/I	0.391	ambiguous	0.4454	ambiguous	0.54	Stabilizing	0.999	D	0.79	deleterious	N	0.482101422	None	None	N
K/L	0.4266	ambiguous	0.4975	ambiguous	0.54	Stabilizing	0.999	D	0.703	prob.delet.	None	None	None	None	N
K/M	0.3018	likely_benign	0.3569	ambiguous	0.209	Stabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
K/N	0.6993	likely_pathogenic	0.751	pathogenic	0.055	Stabilizing	0.999	D	0.771	deleterious	N	0.470007253	None	None	N
K/P	0.7786	likely_pathogenic	0.8711	pathogenic	0.368	Stabilizing	0.999	D	0.796	deleterious	None	None	None	None	N
K/Q	0.1911	likely_benign	0.2314	benign	-0.058	Destabilizing	0.999	D	0.779	deleterious	N	0.497302948	None	None	N
K/R	0.0889	likely_benign	0.096	benign	-0.162	Destabilizing	0.997	D	0.77	deleterious	N	0.44793292	None	None	N
K/S	0.6621	likely_pathogenic	0.7352	pathogenic	-0.477	Destabilizing	0.998	D	0.793	deleterious	None	None	None	None	N
K/T	0.241	likely_benign	0.2857	benign	-0.265	Destabilizing	0.999	D	0.776	deleterious	N	0.431443315	None	None	N
K/V	0.3549	ambiguous	0.4125	ambiguous	0.368	Stabilizing	0.999	D	0.771	deleterious	None	None	None	None	N
K/W	0.8337	likely_pathogenic	0.8815	pathogenic	-0.063	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
K/Y	0.734	likely_pathogenic	0.7841	pathogenic	0.268	Stabilizing	1.0	D	0.791	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.