TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27436	82531;82532;82533	chr2:178563826;178563825;178563824	chr2:179428553;179428552;179428551
N2AB	25795	77608;77609;77610	chr2:178563826;178563825;178563824	chr2:179428553;179428552;179428551
N2A	24868	74827;74828;74829	chr2:178563826;178563825;178563824	chr2:179428553;179428552;179428551
N2B	18371	55336;55337;55338	chr2:178563826;178563825;178563824	chr2:179428553;179428552;179428551
Novex-1	18496	55711;55712;55713	chr2:178563826;178563825;178563824	chr2:179428553;179428552;179428551
Novex-2	18563	55912;55913;55914	chr2:178563826;178563825;178563824	chr2:179428553;179428552;179428551
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-87
• Domain position: 68
• Structural Position: 99
• Q(SASA): 0.5803
• 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
P/S	None	None	0.521	D	0.376	0.336	0.269558022972	gnomAD-4.0.0	3.18268E-06	None	None	None	None	N	None	0	0	None	0	5.5497E-05	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
P/A	0.0675	likely_benign	0.0693	benign	-0.828	Destabilizing	0.007	N	0.234	neutral	N	0.518127377	None	None	N
P/C	0.3973	ambiguous	0.4362	ambiguous	-0.589	Destabilizing	0.996	D	0.505	neutral	None	None	None	None	N
P/D	0.5097	ambiguous	0.5295	ambiguous	-0.683	Destabilizing	0.59	D	0.456	neutral	None	None	None	None	N
P/E	0.2258	likely_benign	0.2357	benign	-0.791	Destabilizing	0.082	N	0.251	neutral	None	None	None	None	N
P/F	0.4911	ambiguous	0.5159	ambiguous	-0.977	Destabilizing	0.953	D	0.507	neutral	None	None	None	None	N
P/G	0.3002	likely_benign	0.305	benign	-1.002	Destabilizing	0.009	N	0.245	neutral	None	None	None	None	N
P/H	0.1865	likely_benign	0.1951	benign	-0.524	Destabilizing	0.994	D	0.467	neutral	N	0.509903559	None	None	N
P/I	0.2509	likely_benign	0.2746	benign	-0.507	Destabilizing	0.91	D	0.51	neutral	None	None	None	None	N
P/K	0.2129	likely_benign	0.2187	benign	-0.66	Destabilizing	0.742	D	0.455	neutral	None	None	None	None	N
P/L	0.1057	likely_benign	0.1114	benign	-0.507	Destabilizing	0.521	D	0.506	neutral	N	0.495660418	None	None	N
P/M	0.2424	likely_benign	0.2631	benign	-0.326	Destabilizing	0.996	D	0.465	neutral	None	None	None	None	N
P/N	0.3286	likely_benign	0.3524	ambiguous	-0.337	Destabilizing	0.91	D	0.477	neutral	None	None	None	None	N
P/Q	0.1276	likely_benign	0.1377	benign	-0.634	Destabilizing	0.91	D	0.434	neutral	None	None	None	None	N
P/R	0.1569	likely_benign	0.1583	benign	-0.039	Destabilizing	0.884	D	0.473	neutral	N	0.496559017	None	None	N
P/S	0.1299	likely_benign	0.1377	benign	-0.718	Destabilizing	0.521	D	0.376	neutral	D	0.53377162	None	None	N
P/T	0.0862	likely_benign	0.0947	benign	-0.729	Destabilizing	0.028	N	0.255	neutral	D	0.53377162	None	None	N
P/V	0.1607	likely_benign	0.1714	benign	-0.578	Destabilizing	0.59	D	0.481	neutral	None	None	None	None	N
P/W	0.6079	likely_pathogenic	0.627	pathogenic	-1.047	Destabilizing	0.996	D	0.572	neutral	None	None	None	None	N
P/Y	0.4179	ambiguous	0.4336	ambiguous	-0.762	Destabilizing	0.984	D	0.511	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.