TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3019	9280;9281;9282	chr2:178768781;178768780;178768779	chr2:179633508;179633507;179633506
N2AB	3019	9280;9281;9282	chr2:178768781;178768780;178768779	chr2:179633508;179633507;179633506
N2A	3019	9280;9281;9282	chr2:178768781;178768780;178768779	chr2:179633508;179633507;179633506
N2B	2973	9142;9143;9144	chr2:178768781;178768780;178768779	chr2:179633508;179633507;179633506
Novex-1	2973	9142;9143;9144	chr2:178768781;178768780;178768779	chr2:179633508;179633507;179633506
Novex-2	2973	9142;9143;9144	chr2:178768781;178768780;178768779	chr2:179633508;179633507;179633506
Novex-3	3019	9280;9281;9282	chr2:178768781;178768780;178768779	chr2:179633508;179633507;179633506

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-20
• Domain position: 51
• Structural Position: 130
• Q(SASA): 0.3749
• 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	None	None	0.217	N	0.212	0.19	0.203808441222	gnomAD-4.0.0	1.59058E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85651E-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	0.7546	likely_pathogenic	0.815	pathogenic	0.04	Stabilizing	0.996	D	0.479	neutral	None	None	None	None	N
K/C	0.9199	likely_pathogenic	0.9478	pathogenic	-0.231	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
K/D	0.8539	likely_pathogenic	0.9061	pathogenic	-0.048	Destabilizing	0.999	D	0.553	neutral	None	None	None	None	N
K/E	0.496	ambiguous	0.6161	pathogenic	-0.062	Destabilizing	0.989	D	0.439	neutral	N	0.472926702	None	None	N
K/F	0.9644	likely_pathogenic	0.9805	pathogenic	-0.288	Destabilizing	1.0	D	0.623	neutral	None	None	None	None	N
K/G	0.7549	likely_pathogenic	0.8056	pathogenic	-0.114	Destabilizing	0.999	D	0.477	neutral	None	None	None	None	N
K/H	0.5913	likely_pathogenic	0.6721	pathogenic	-0.367	Destabilizing	1.0	D	0.552	neutral	None	None	None	None	N
K/I	0.8054	likely_pathogenic	0.8674	pathogenic	0.357	Stabilizing	0.999	D	0.638	neutral	N	0.502000061	None	None	N
K/L	0.8018	likely_pathogenic	0.8489	pathogenic	0.357	Stabilizing	0.999	D	0.477	neutral	None	None	None	None	N
K/M	0.6845	likely_pathogenic	0.7657	pathogenic	0.176	Stabilizing	1.0	D	0.551	neutral	None	None	None	None	N
K/N	0.7691	likely_pathogenic	0.8461	pathogenic	0.231	Stabilizing	0.998	D	0.496	neutral	N	0.511408116	None	None	N
K/P	0.9608	likely_pathogenic	0.9671	pathogenic	0.277	Stabilizing	1.0	D	0.538	neutral	None	None	None	None	N
K/Q	0.2874	likely_benign	0.3541	ambiguous	0.039	Stabilizing	0.997	D	0.504	neutral	N	0.500487266	None	None	N
K/R	0.0828	likely_benign	0.0882	benign	0.002	Stabilizing	0.217	N	0.212	neutral	N	0.499629082	None	None	N
K/S	0.7668	likely_pathogenic	0.8338	pathogenic	-0.206	Destabilizing	0.996	D	0.443	neutral	None	None	None	None	N
K/T	0.578	likely_pathogenic	0.6665	pathogenic	-0.09	Destabilizing	0.998	D	0.503	neutral	N	0.503016513	None	None	N
K/V	0.7333	likely_pathogenic	0.7973	pathogenic	0.277	Stabilizing	0.999	D	0.583	neutral	None	None	None	None	N
K/W	0.9164	likely_pathogenic	0.9486	pathogenic	-0.336	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
K/Y	0.8929	likely_pathogenic	0.9337	pathogenic	0.031	Stabilizing	1.0	D	0.591	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.