TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32074	96445;96446;96447	chr2:178543924;178543923;178543922	chr2:179408651;179408650;179408649
N2AB	30433	91522;91523;91524	chr2:178543924;178543923;178543922	chr2:179408651;179408650;179408649
N2A	29506	88741;88742;88743	chr2:178543924;178543923;178543922	chr2:179408651;179408650;179408649
N2B	23009	69250;69251;69252	chr2:178543924;178543923;178543922	chr2:179408651;179408650;179408649
Novex-1	23134	69625;69626;69627	chr2:178543924;178543923;178543922	chr2:179408651;179408650;179408649
Novex-2	23201	69826;69827;69828	chr2:178543924;178543923;178543922	chr2:179408651;179408650;179408649
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-153
• Domain position: 58
• Structural Position: 143
• Q(SASA): 0.7635
• 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	0.998	N	0.546	0.235	0.152612264143	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.4019	ambiguous	0.3638	ambiguous	0.044	Stabilizing	0.998	D	0.588	neutral	None	None	None	None	N
K/C	0.6637	likely_pathogenic	0.6457	pathogenic	-0.096	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
K/D	0.4497	ambiguous	0.4195	ambiguous	0.11	Stabilizing	0.998	D	0.575	neutral	None	None	None	None	N
K/E	0.2353	likely_benign	0.2154	benign	0.093	Stabilizing	0.996	D	0.516	neutral	N	0.455400397	None	None	N
K/F	0.8461	likely_pathogenic	0.8141	pathogenic	-0.326	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	N
K/G	0.4161	ambiguous	0.3807	ambiguous	-0.113	Destabilizing	0.997	D	0.534	neutral	None	None	None	None	N
K/H	0.2566	likely_benign	0.2548	benign	-0.439	Destabilizing	1.0	D	0.609	neutral	None	None	None	None	N
K/I	0.6166	likely_pathogenic	0.5627	ambiguous	0.366	Stabilizing	1.0	D	0.691	prob.neutral	N	0.473026355	None	None	N
K/L	0.5537	ambiguous	0.4937	ambiguous	0.366	Stabilizing	1.0	D	0.549	neutral	None	None	None	None	N
K/M	0.3398	likely_benign	0.3016	benign	0.327	Stabilizing	1.0	D	0.617	neutral	None	None	None	None	N
K/N	0.323	likely_benign	0.2955	benign	0.418	Stabilizing	0.884	D	0.343	neutral	N	0.379822416	None	None	N
K/P	0.8836	likely_pathogenic	0.8613	pathogenic	0.285	Stabilizing	1.0	D	0.611	neutral	None	None	None	None	N
K/Q	0.1545	likely_benign	0.1476	benign	0.178	Stabilizing	0.999	D	0.649	neutral	N	0.477989255	None	None	N
K/R	0.0852	likely_benign	0.0853	benign	0.176	Stabilizing	0.998	D	0.546	neutral	N	0.456632548	None	None	N
K/S	0.3909	ambiguous	0.3594	ambiguous	-0.076	Destabilizing	0.997	D	0.537	neutral	None	None	None	None	N
K/T	0.2226	likely_benign	0.2015	benign	0.041	Stabilizing	0.999	D	0.593	neutral	N	0.505637217	None	None	N
K/V	0.5189	ambiguous	0.4647	ambiguous	0.285	Stabilizing	1.0	D	0.617	neutral	None	None	None	None	N
K/W	0.8088	likely_pathogenic	0.7879	pathogenic	-0.341	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
K/Y	0.6379	likely_pathogenic	0.6074	pathogenic	0.044	Stabilizing	1.0	D	0.644	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.