TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24079	72460;72461;72462	chr2:178573897;178573896;178573895	chr2:179438624;179438623;179438622
N2AB	22438	67537;67538;67539	chr2:178573897;178573896;178573895	chr2:179438624;179438623;179438622
N2A	21511	64756;64757;64758	chr2:178573897;178573896;178573895	chr2:179438624;179438623;179438622
N2B	15014	45265;45266;45267	chr2:178573897;178573896;178573895	chr2:179438624;179438623;179438622
Novex-1	15139	45640;45641;45642	chr2:178573897;178573896;178573895	chr2:179438624;179438623;179438622
Novex-2	15206	45841;45842;45843	chr2:178573897;178573896;178573895	chr2:179438624;179438623;179438622
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: Ig-131
• Domain position: 51
• Structural Position: 125
• Q(SASA): 0.5306
• 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/R	rs775482499	-0.039	0.01	N	0.293	0.102	0.368554958709	gnomAD-2.1.1	2.02E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.64031E-04	None	0	0	0
K/R	rs775482499	-0.039	0.01	N	0.293	0.102	0.368554958709	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	6.21375E-04	0
K/R	rs775482499	-0.039	0.01	N	0.293	0.102	0.368554958709	gnomAD-4.0.0	1.55153E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.74804E-04	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	0.3532	ambiguous	0.3031	benign	-0.173	Destabilizing	0.648	D	0.582	neutral	None	None	None	None	N
K/C	0.6365	likely_pathogenic	0.5508	ambiguous	-0.269	Destabilizing	0.993	D	0.685	prob.neutral	None	None	None	None	N
K/D	0.5918	likely_pathogenic	0.5171	ambiguous	0.117	Stabilizing	0.866	D	0.691	prob.neutral	None	None	None	None	N
K/E	0.2005	likely_benign	0.1785	benign	0.164	Stabilizing	0.41	N	0.523	neutral	N	0.45542548	None	None	N
K/F	0.7283	likely_pathogenic	0.6669	pathogenic	-0.122	Destabilizing	0.98	D	0.671	neutral	None	None	None	None	N
K/G	0.509	ambiguous	0.4338	ambiguous	-0.458	Destabilizing	0.866	D	0.574	neutral	None	None	None	None	N
K/H	0.243	likely_benign	0.2055	benign	-0.814	Destabilizing	0.98	D	0.657	neutral	None	None	None	None	N
K/I	0.2782	likely_benign	0.2442	benign	0.523	Stabilizing	0.908	D	0.698	prob.neutral	N	0.489116766	None	None	N
K/L	0.3364	likely_benign	0.2959	benign	0.523	Stabilizing	0.866	D	0.574	neutral	None	None	None	None	N
K/M	0.2105	likely_benign	0.1855	benign	0.353	Stabilizing	0.993	D	0.657	neutral	None	None	None	None	N
K/N	0.3783	ambiguous	0.3301	benign	0.031	Stabilizing	0.83	D	0.618	neutral	N	0.489304089	None	None	N
K/P	0.9088	likely_pathogenic	0.8823	pathogenic	0.322	Stabilizing	0.929	D	0.687	prob.neutral	None	None	None	None	N
K/Q	0.1222	likely_benign	0.1115	benign	-0.123	Destabilizing	0.709	D	0.605	neutral	N	0.509278607	None	None	N
K/R	0.0796	likely_benign	0.0749	benign	-0.286	Destabilizing	0.01	N	0.293	neutral	N	0.49482923	None	None	N
K/S	0.3758	ambiguous	0.3306	benign	-0.548	Destabilizing	0.648	D	0.574	neutral	None	None	None	None	N
K/T	0.1452	likely_benign	0.1251	benign	-0.326	Destabilizing	0.83	D	0.657	neutral	N	0.438127798	None	None	N
K/V	0.2755	likely_benign	0.2431	benign	0.322	Stabilizing	0.866	D	0.672	neutral	None	None	None	None	N
K/W	0.7222	likely_pathogenic	0.6333	pathogenic	-0.05	Destabilizing	0.993	D	0.689	prob.neutral	None	None	None	None	N
K/Y	0.6132	likely_pathogenic	0.5415	ambiguous	0.264	Stabilizing	0.929	D	0.665	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.