TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1600	5023;5024;5025	chr2:178777165;178777164;178777163	chr2:179641892;179641891;179641890
N2AB	1600	5023;5024;5025	chr2:178777165;178777164;178777163	chr2:179641892;179641891;179641890
N2A	1600	5023;5024;5025	chr2:178777165;178777164;178777163	chr2:179641892;179641891;179641890
N2B	1554	4885;4886;4887	chr2:178777165;178777164;178777163	chr2:179641892;179641891;179641890
Novex-1	1554	4885;4886;4887	chr2:178777165;178777164;178777163	chr2:179641892;179641891;179641890
Novex-2	1554	4885;4886;4887	chr2:178777165;178777164;178777163	chr2:179641892;179641891;179641890
Novex-3	1600	5023;5024;5025	chr2:178777165;178777164;178777163	chr2:179641892;179641891;179641890

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-7
• Domain position: 45
• Structural Position: 109
• Q(SASA): 0.3669
• 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/E	None	None	0.999	N	0.553	0.39	0.242244723065	gnomAD-4.0.0	1.59064E-06	None	None	None	None	N	None	0	2.28634E-05	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
K/A	0.8909	likely_pathogenic	0.7963	pathogenic	-0.375	Destabilizing	0.999	D	0.57	neutral	None	None	None	None	N
K/C	0.9524	likely_pathogenic	0.9156	pathogenic	-0.472	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
K/D	0.9667	likely_pathogenic	0.9327	pathogenic	0.128	Stabilizing	1.0	D	0.622	neutral	None	None	None	None	N
K/E	0.8083	likely_pathogenic	0.6693	pathogenic	0.234	Stabilizing	0.999	D	0.553	neutral	N	0.443384459	None	None	N
K/F	0.9826	likely_pathogenic	0.9648	pathogenic	-0.168	Destabilizing	1.0	D	0.644	neutral	None	None	None	None	N
K/G	0.9441	likely_pathogenic	0.8941	pathogenic	-0.701	Destabilizing	1.0	D	0.565	neutral	None	None	None	None	N
K/H	0.6569	likely_pathogenic	0.5668	pathogenic	-0.909	Destabilizing	1.0	D	0.618	neutral	None	None	None	None	N
K/I	0.8057	likely_pathogenic	0.7055	pathogenic	0.453	Stabilizing	1.0	D	0.668	neutral	N	0.507103108	None	None	N
K/L	0.7842	likely_pathogenic	0.6839	pathogenic	0.453	Stabilizing	1.0	D	0.565	neutral	None	None	None	None	N
K/M	0.7404	likely_pathogenic	0.6181	pathogenic	0.081	Stabilizing	1.0	D	0.611	neutral	None	None	None	None	N
K/N	0.8973	likely_pathogenic	0.819	pathogenic	-0.278	Destabilizing	1.0	D	0.661	neutral	N	0.44948919	None	None	N
K/P	0.9874	likely_pathogenic	0.9736	pathogenic	0.207	Stabilizing	1.0	D	0.612	neutral	None	None	None	None	N
K/Q	0.4624	ambiguous	0.3511	ambiguous	-0.265	Destabilizing	1.0	D	0.657	neutral	N	0.485912603	None	None	N
K/R	0.1186	likely_benign	0.1078	benign	-0.348	Destabilizing	0.999	D	0.501	neutral	N	0.449976972	None	None	N
K/S	0.9206	likely_pathogenic	0.8524	pathogenic	-0.855	Destabilizing	0.999	D	0.581	neutral	None	None	None	None	N
K/T	0.7052	likely_pathogenic	0.5694	pathogenic	-0.548	Destabilizing	1.0	D	0.604	neutral	N	0.447692965	None	None	N
K/V	0.7944	likely_pathogenic	0.6923	pathogenic	0.207	Stabilizing	1.0	D	0.607	neutral	None	None	None	None	N
K/W	0.9714	likely_pathogenic	0.9502	pathogenic	-0.134	Destabilizing	1.0	D	0.668	neutral	None	None	None	None	N
K/Y	0.9377	likely_pathogenic	0.8934	pathogenic	0.174	Stabilizing	1.0	D	0.604	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.