TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31502	94729;94730;94731	chr2:178547021;178547020;178547019	chr2:179411748;179411747;179411746
N2AB	29861	89806;89807;89808	chr2:178547021;178547020;178547019	chr2:179411748;179411747;179411746
N2A	28934	87025;87026;87027	chr2:178547021;178547020;178547019	chr2:179411748;179411747;179411746
N2B	22437	67534;67535;67536	chr2:178547021;178547020;178547019	chr2:179411748;179411747;179411746
Novex-1	22562	67909;67910;67911	chr2:178547021;178547020;178547019	chr2:179411748;179411747;179411746
Novex-2	22629	68110;68111;68112	chr2:178547021;178547020;178547019	chr2:179411748;179411747;179411746
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Fn3-117
• Domain position: 95
• Structural Position: 129
• Q(SASA): 0.3656
• 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
M/T	None	None	0.023	N	0.391	0.243	0.413241256734	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-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
M/A	0.2936	likely_benign	0.2985	benign	-1.272	Destabilizing	0.003	N	0.287	neutral	None	None	None	None	N
M/C	0.656	likely_pathogenic	0.6694	pathogenic	-1.017	Destabilizing	0.352	N	0.332	neutral	None	None	None	None	N
M/D	0.9108	likely_pathogenic	0.9298	pathogenic	-0.244	Destabilizing	0.134	N	0.649	prob.neutral	None	None	None	None	N
M/E	0.6354	likely_pathogenic	0.7014	pathogenic	-0.249	Destabilizing	0.134	N	0.477	neutral	None	None	None	None	N
M/F	0.3752	ambiguous	0.4009	ambiguous	-0.459	Destabilizing	0.071	N	0.224	neutral	None	None	None	None	N
M/G	0.6568	likely_pathogenic	0.6627	pathogenic	-1.539	Destabilizing	0.06	N	0.421	neutral	None	None	None	None	N
M/H	0.5983	likely_pathogenic	0.6269	pathogenic	-0.526	Destabilizing	0.624	D	0.44	neutral	None	None	None	None	N
M/I	0.2245	likely_benign	0.2547	benign	-0.617	Destabilizing	0.001	N	0.169	neutral	N	0.396128381	None	None	N
M/K	0.2506	likely_benign	0.2877	benign	-0.236	Destabilizing	0.046	N	0.328	neutral	N	0.387567613	None	None	N
M/L	0.103	likely_benign	0.1025	benign	-0.617	Destabilizing	None	N	0.037	neutral	N	0.356185913	None	None	N
M/N	0.5945	likely_pathogenic	0.6349	pathogenic	-0.105	Destabilizing	0.321	N	0.635	neutral	None	None	None	None	N
M/P	0.5076	ambiguous	0.5447	ambiguous	-0.807	Destabilizing	0.321	N	0.606	neutral	None	None	None	None	N
M/Q	0.3006	likely_benign	0.3141	benign	-0.239	Destabilizing	0.321	N	0.384	neutral	None	None	None	None	N
M/R	0.2495	likely_benign	0.2812	benign	0.328	Stabilizing	0.105	N	0.505	neutral	N	0.406153374	None	None	N
M/S	0.443	ambiguous	0.4597	ambiguous	-0.67	Destabilizing	0.031	N	0.325	neutral	None	None	None	None	N
M/T	0.1429	likely_benign	0.1581	benign	-0.566	Destabilizing	0.023	N	0.391	neutral	N	0.321755548	None	None	N
M/V	0.0607	likely_benign	0.0631	benign	-0.807	Destabilizing	None	N	0.047	neutral	N	0.31022155	None	None	N
M/W	0.7164	likely_pathogenic	0.7353	pathogenic	-0.376	Destabilizing	0.862	D	0.352	neutral	None	None	None	None	N
M/Y	0.655	likely_pathogenic	0.69	pathogenic	-0.36	Destabilizing	0.134	N	0.505	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.