TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14063	42412;42413;42414	chr2:178634594;178634593;178634592	chr2:179499321;179499320;179499319
N2AB	12422	37489;37490;37491	chr2:178634594;178634593;178634592	chr2:179499321;179499320;179499319
N2A	11495	34708;34709;34710	chr2:178634594;178634593;178634592	chr2:179499321;179499320;179499319
N2B	4998	15217;15218;15219	chr2:178634594;178634593;178634592	chr2:179499321;179499320;179499319
Novex-1	5123	15592;15593;15594	chr2:178634594;178634593;178634592	chr2:179499321;179499320;179499319
Novex-2	5190	15793;15794;15795	chr2:178634594;178634593;178634592	chr2:179499321;179499320;179499319
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-91
• Domain position: 10
• Structural Position: 13
• Q(SASA): 0.2224
• 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/A	rs772758022	-1.448	0.989	D	0.443	0.463	0.676012115908	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
V/A	rs772758022	-1.448	0.989	D	0.443	0.463	0.676012115908	gnomAD-4.0.0	3.18445E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72037E-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
V/A	0.5856	likely_pathogenic	0.5388	ambiguous	-1.37	Destabilizing	0.989	D	0.443	neutral	D	0.540625622	None	None	N
V/C	0.9451	likely_pathogenic	0.9189	pathogenic	-0.734	Destabilizing	1.0	D	0.526	neutral	None	None	None	None	N
V/D	0.9019	likely_pathogenic	0.8806	pathogenic	-1.515	Destabilizing	0.997	D	0.677	prob.neutral	D	0.690643495	None	None	N
V/E	0.7115	likely_pathogenic	0.6833	pathogenic	-1.386	Destabilizing	0.995	D	0.574	neutral	None	None	None	None	N
V/F	0.6185	likely_pathogenic	0.5848	pathogenic	-0.828	Destabilizing	0.998	D	0.551	neutral	D	0.650213858	None	None	N
V/G	0.8117	likely_pathogenic	0.7791	pathogenic	-1.808	Destabilizing	0.998	D	0.654	neutral	D	0.689945481	None	None	N
V/H	0.9452	likely_pathogenic	0.9397	pathogenic	-1.546	Destabilizing	1.0	D	0.67	neutral	None	None	None	None	N
V/I	0.0902	likely_benign	0.0883	benign	-0.211	Destabilizing	0.543	D	0.319	neutral	N	0.519733244	None	None	N
V/K	0.7816	likely_pathogenic	0.7684	pathogenic	-1.078	Destabilizing	0.995	D	0.572	neutral	None	None	None	None	N
V/L	0.5769	likely_pathogenic	0.5208	ambiguous	-0.211	Destabilizing	0.948	D	0.414	neutral	N	0.505314127	None	None	N
V/M	0.3024	likely_benign	0.2879	benign	-0.131	Destabilizing	0.999	D	0.46	neutral	None	None	None	None	N
V/N	0.8119	likely_pathogenic	0.7865	pathogenic	-1.161	Destabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	N
V/P	0.9938	likely_pathogenic	0.9938	pathogenic	-0.564	Destabilizing	1.0	D	0.629	neutral	None	None	None	None	N
V/Q	0.7224	likely_pathogenic	0.7078	pathogenic	-1.124	Destabilizing	0.96	D	0.399	neutral	None	None	None	None	N
V/R	0.7729	likely_pathogenic	0.7607	pathogenic	-0.842	Destabilizing	0.998	D	0.688	prob.neutral	None	None	None	None	N
V/S	0.7582	likely_pathogenic	0.7343	pathogenic	-1.724	Destabilizing	0.998	D	0.567	neutral	None	None	None	None	N
V/T	0.4865	ambiguous	0.4561	ambiguous	-1.47	Destabilizing	0.996	D	0.443	neutral	None	None	None	None	N
V/W	0.9893	likely_pathogenic	0.9868	pathogenic	-1.285	Destabilizing	1.0	D	0.65	neutral	None	None	None	None	N
V/Y	0.9364	likely_pathogenic	0.9233	pathogenic	-0.839	Destabilizing	1.0	D	0.556	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.