TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22202	66829;66830;66831	chr2:178581664;178581663;178581662	chr2:179446391;179446390;179446389
N2AB	20561	61906;61907;61908	chr2:178581664;178581663;178581662	chr2:179446391;179446390;179446389
N2A	19634	59125;59126;59127	chr2:178581664;178581663;178581662	chr2:179446391;179446390;179446389
N2B	13137	39634;39635;39636	chr2:178581664;178581663;178581662	chr2:179446391;179446390;179446389
Novex-1	13262	40009;40010;40011	chr2:178581664;178581663;178581662	chr2:179446391;179446390;179446389
Novex-2	13329	40210;40211;40212	chr2:178581664;178581663;178581662	chr2:179446391;179446390;179446389
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-49
• Domain position: 47
• Structural Position: 64
• Q(SASA): 0.5369
• 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
N/K	rs1224096976	0.353	0.055	N	0.287	0.082	0.141422826196	gnomAD-4.0.0	3.18729E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72403E-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
N/A	0.1508	likely_benign	0.1462	benign	-0.362	Destabilizing	0.016	N	0.311	neutral	None	None	None	None	N
N/C	0.2307	likely_benign	0.2172	benign	0.283	Stabilizing	0.864	D	0.312	neutral	None	None	None	None	N
N/D	0.1107	likely_benign	0.1068	benign	0.194	Stabilizing	None	N	0.101	neutral	N	0.357324851	None	None	N
N/E	0.232	likely_benign	0.2165	benign	0.158	Stabilizing	0.001	N	0.138	neutral	None	None	None	None	N
N/F	0.4417	ambiguous	0.4287	ambiguous	-0.769	Destabilizing	0.214	N	0.333	neutral	None	None	None	None	N
N/G	0.239	likely_benign	0.2332	benign	-0.525	Destabilizing	None	N	0.119	neutral	None	None	None	None	N
N/H	0.0872	likely_benign	0.0858	benign	-0.515	Destabilizing	None	N	0.141	neutral	N	0.423339199	None	None	N
N/I	0.1646	likely_benign	0.1584	benign	-0.022	Destabilizing	0.029	N	0.335	neutral	N	0.42503271	None	None	N
N/K	0.2446	likely_benign	0.2353	benign	0.068	Stabilizing	0.055	N	0.287	neutral	N	0.396805959	None	None	N
N/L	0.1781	likely_benign	0.185	benign	-0.022	Destabilizing	0.038	N	0.356	neutral	None	None	None	None	N
N/M	0.2916	likely_benign	0.2725	benign	0.209	Stabilizing	0.356	N	0.308	neutral	None	None	None	None	N
N/P	0.6222	likely_pathogenic	0.6636	pathogenic	-0.109	Destabilizing	0.136	N	0.355	neutral	None	None	None	None	N
N/Q	0.2233	likely_benign	0.208	benign	-0.314	Destabilizing	0.072	N	0.268	neutral	None	None	None	None	N
N/R	0.2677	likely_benign	0.2614	benign	0.123	Stabilizing	0.072	N	0.273	neutral	None	None	None	None	N
N/S	0.0738	likely_benign	0.0717	benign	-0.129	Destabilizing	0.024	N	0.363	neutral	N	0.394245656	None	None	N
N/T	0.0918	likely_benign	0.0864	benign	-0.022	Destabilizing	0.055	N	0.287	neutral	N	0.389418626	None	None	N
N/V	0.1602	likely_benign	0.1525	benign	-0.109	Destabilizing	0.001	N	0.342	neutral	None	None	None	None	N
N/W	0.7406	likely_pathogenic	0.7265	pathogenic	-0.783	Destabilizing	0.864	D	0.326	neutral	None	None	None	None	N
N/Y	0.1559	likely_benign	0.1578	benign	-0.511	Destabilizing	0.093	N	0.335	neutral	N	0.467226049	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.