TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17623	53092;53093;53094	chr2:178607920;178607919;178607918	chr2:179472647;179472646;179472645
N2AB	15982	48169;48170;48171	chr2:178607920;178607919;178607918	chr2:179472647;179472646;179472645
N2A	15055	45388;45389;45390	chr2:178607920;178607919;178607918	chr2:179472647;179472646;179472645
N2B	8558	25897;25898;25899	chr2:178607920;178607919;178607918	chr2:179472647;179472646;179472645
Novex-1	8683	26272;26273;26274	chr2:178607920;178607919;178607918	chr2:179472647;179472646;179472645
Novex-2	8750	26473;26474;26475	chr2:178607920;178607919;178607918	chr2:179472647;179472646;179472645
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: Fn3-16
• Domain position: 55
• Structural Position: 75
• Q(SASA): 0.2614
• 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	rs2055311301	None	0.425	N	0.346	0.2	0.667830379453	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
M/T	rs2055311301	None	0.425	N	0.346	0.2	0.667830379453	gnomAD-4.0.0	2.56481E-06	None	None	None	None	N	None	1.69342E-05	0	None	0	0	None	0	0	2.39559E-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	0.1809	likely_benign	0.1704	benign	-1.386	Destabilizing	0.3	N	0.22	neutral	None	None	None	None	N
M/C	0.5461	ambiguous	0.5465	ambiguous	-1.031	Destabilizing	0.981	D	0.329	neutral	None	None	None	None	N
M/D	0.7245	likely_pathogenic	0.6808	pathogenic	-0.146	Destabilizing	0.828	D	0.374	neutral	None	None	None	None	N
M/E	0.3251	likely_benign	0.3053	benign	-0.088	Destabilizing	0.495	N	0.345	neutral	None	None	None	None	N
M/F	0.4149	ambiguous	0.3828	ambiguous	-0.326	Destabilizing	0.704	D	0.212	neutral	None	None	None	None	N
M/G	0.4399	ambiguous	0.4103	ambiguous	-1.701	Destabilizing	0.495	N	0.345	neutral	None	None	None	None	N
M/H	0.4654	ambiguous	0.4285	ambiguous	-0.62	Destabilizing	0.981	D	0.369	neutral	None	None	None	None	N
M/I	0.2393	likely_benign	0.2143	benign	-0.572	Destabilizing	0.139	N	0.237	neutral	N	0.394997805	None	None	N
M/K	0.1627	likely_benign	0.136	benign	-0.337	Destabilizing	0.425	N	0.328	neutral	N	0.376755973	None	None	N
M/L	0.1151	likely_benign	0.1049	benign	-0.572	Destabilizing	0.001	N	0.054	neutral	N	0.356247415	None	None	N
M/N	0.3144	likely_benign	0.2973	benign	-0.328	Destabilizing	0.828	D	0.437	neutral	None	None	None	None	N
M/P	0.1279	likely_benign	0.1362	benign	-0.817	Destabilizing	0.001	N	0.177	neutral	None	None	None	None	N
M/Q	0.1662	likely_benign	0.1576	benign	-0.335	Destabilizing	0.828	D	0.211	neutral	None	None	None	None	N
M/R	0.1727	likely_benign	0.1439	benign	0.104	Stabilizing	0.784	D	0.349	neutral	N	0.35597527	None	None	N
M/S	0.2755	likely_benign	0.2664	benign	-0.945	Destabilizing	0.495	N	0.345	neutral	None	None	None	None	N
M/T	0.1713	likely_benign	0.1492	benign	-0.77	Destabilizing	0.425	N	0.346	neutral	N	0.370947509	None	None	N
M/V	0.0917	likely_benign	0.087	benign	-0.817	Destabilizing	0.139	N	0.201	neutral	N	0.38907191	None	None	N
M/W	0.63	likely_pathogenic	0.6087	pathogenic	-0.297	Destabilizing	0.995	D	0.301	neutral	None	None	None	None	N
M/Y	0.5194	ambiguous	0.4902	ambiguous	-0.292	Destabilizing	0.936	D	0.405	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.