TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14389	43390;43391;43392	chr2:178632966;178632965;178632964	chr2:179497693;179497692;179497691
N2AB	12748	38467;38468;38469	chr2:178632966;178632965;178632964	chr2:179497693;179497692;179497691
N2A	11821	35686;35687;35688	chr2:178632966;178632965;178632964	chr2:179497693;179497692;179497691
N2B	5324	16195;16196;16197	chr2:178632966;178632965;178632964	chr2:179497693;179497692;179497691
Novex-1	5449	16570;16571;16572	chr2:178632966;178632965;178632964	chr2:179497693;179497692;179497691
Novex-2	5516	16771;16772;16773	chr2:178632966;178632965;178632964	chr2:179497693;179497692;179497691
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-94
• Domain position: 71
• Structural Position: 155
• Q(SASA): 0.1163
• 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
S/P	None	None	0.996	N	0.755	0.249	0.295974979623	gnomAD-4.0.0	1.59255E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8608E-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
S/A	0.1064	likely_benign	0.1024	benign	-1.046	Destabilizing	0.057	N	0.339	neutral	N	0.43655841	None	None	N
S/C	0.1568	likely_benign	0.1783	benign	-0.781	Destabilizing	0.073	N	0.492	neutral	N	0.428429499	None	None	N
S/D	0.6331	likely_pathogenic	0.6522	pathogenic	-1.108	Destabilizing	0.967	D	0.65	prob.neutral	None	None	None	None	N
S/E	0.6265	likely_pathogenic	0.623	pathogenic	-0.928	Destabilizing	0.967	D	0.638	neutral	None	None	None	None	N
S/F	0.2321	likely_benign	0.2324	benign	-1.002	Destabilizing	0.987	D	0.659	prob.neutral	N	0.508384181	None	None	N
S/G	0.1722	likely_benign	0.1646	benign	-1.421	Destabilizing	0.018	N	0.337	neutral	None	None	None	None	N
S/H	0.4808	ambiguous	0.4865	ambiguous	-1.646	Destabilizing	0.999	D	0.66	prob.neutral	None	None	None	None	N
S/I	0.1599	likely_benign	0.1645	benign	-0.093	Destabilizing	0.877	D	0.647	neutral	None	None	None	None	N
S/K	0.8493	likely_pathogenic	0.8479	pathogenic	-0.11	Destabilizing	0.967	D	0.64	neutral	None	None	None	None	N
S/L	0.1335	likely_benign	0.1312	benign	-0.093	Destabilizing	0.747	D	0.596	neutral	None	None	None	None	N
S/M	0.274	likely_benign	0.2592	benign	-0.175	Destabilizing	0.99	D	0.673	prob.neutral	None	None	None	None	N
S/N	0.2442	likely_benign	0.2443	benign	-0.722	Destabilizing	0.967	D	0.639	neutral	None	None	None	None	N
S/P	0.9503	likely_pathogenic	0.9546	pathogenic	-0.377	Destabilizing	0.996	D	0.755	deleterious	N	0.510129912	None	None	N
S/Q	0.6614	likely_pathogenic	0.6495	pathogenic	-0.572	Destabilizing	0.997	D	0.666	prob.neutral	None	None	None	None	N
S/R	0.7289	likely_pathogenic	0.7387	pathogenic	-0.402	Destabilizing	0.99	D	0.747	deleterious	None	None	None	None	N
S/T	0.09	likely_benign	0.0872	benign	-0.519	Destabilizing	0.817	D	0.514	neutral	N	0.41537228	None	None	N
S/V	0.2042	likely_benign	0.2024	benign	-0.377	Destabilizing	0.161	N	0.508	neutral	None	None	None	None	N
S/W	0.4647	ambiguous	0.4911	ambiguous	-1.103	Destabilizing	0.999	D	0.671	prob.neutral	None	None	None	None	N
S/Y	0.2353	likely_benign	0.2511	benign	-0.692	Destabilizing	0.996	D	0.64	neutral	N	0.419612699	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.