TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27316	82171;82172;82173	chr2:178564186;178564185;178564184	chr2:179428913;179428912;179428911
N2AB	25675	77248;77249;77250	chr2:178564186;178564185;178564184	chr2:179428913;179428912;179428911
N2A	24748	74467;74468;74469	chr2:178564186;178564185;178564184	chr2:179428913;179428912;179428911
N2B	18251	54976;54977;54978	chr2:178564186;178564185;178564184	chr2:179428913;179428912;179428911
Novex-1	18376	55351;55352;55353	chr2:178564186;178564185;178564184	chr2:179428913;179428912;179428911
Novex-2	18443	55552;55553;55554	chr2:178564186;178564185;178564184	chr2:179428913;179428912;179428911
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-140
• Domain position: 39
• Structural Position: 58
• Q(SASA): 0.4083
• 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
L/F	rs1704772471	None	0.059	N	0.211	0.289	0.566810639971	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
L/F	rs1704772471	None	0.059	N	0.211	0.289	0.566810639971	gnomAD-4.0.0	6.57488E-06	None	None	None	None	N	None	0	6.55566E-05	None	0	0	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
L/A	0.3495	ambiguous	0.3662	ambiguous	-2.099	Highly Destabilizing	0.919	D	0.346	neutral	None	None	None	None	N
L/C	0.6067	likely_pathogenic	0.6584	pathogenic	-1.465	Destabilizing	0.999	D	0.44	neutral	None	None	None	None	N
L/D	0.887	likely_pathogenic	0.9253	pathogenic	-1.354	Destabilizing	0.996	D	0.519	neutral	None	None	None	None	N
L/E	0.6419	likely_pathogenic	0.7242	pathogenic	-1.258	Destabilizing	0.996	D	0.509	neutral	None	None	None	None	N
L/F	0.1639	likely_benign	0.1869	benign	-1.335	Destabilizing	0.059	N	0.211	neutral	N	0.493705997	None	None	N
L/G	0.7178	likely_pathogenic	0.7725	pathogenic	-2.515	Highly Destabilizing	0.988	D	0.483	neutral	None	None	None	None	N
L/H	0.5328	ambiguous	0.6256	pathogenic	-1.575	Destabilizing	0.999	D	0.529	neutral	D	0.534220148	None	None	N
L/I	0.0775	likely_benign	0.0726	benign	-0.973	Destabilizing	0.046	N	0.137	neutral	N	0.451830601	None	None	N
L/K	0.5625	ambiguous	0.6614	pathogenic	-1.489	Destabilizing	0.996	D	0.466	neutral	None	None	None	None	N
L/M	0.1081	likely_benign	0.1156	benign	-0.9	Destabilizing	0.988	D	0.449	neutral	None	None	None	None	N
L/N	0.6965	likely_pathogenic	0.7791	pathogenic	-1.448	Destabilizing	0.996	D	0.521	neutral	None	None	None	None	N
L/P	0.563	ambiguous	0.5866	pathogenic	-1.321	Destabilizing	0.995	D	0.521	neutral	D	0.533966658	None	None	N
L/Q	0.3966	ambiguous	0.4963	ambiguous	-1.477	Destabilizing	0.996	D	0.484	neutral	None	None	None	None	N
L/R	0.4631	ambiguous	0.5573	ambiguous	-1.011	Destabilizing	0.995	D	0.478	neutral	D	0.545322964	None	None	N
L/S	0.564	ambiguous	0.6402	pathogenic	-2.18	Highly Destabilizing	0.988	D	0.406	neutral	None	None	None	None	N
L/T	0.3086	likely_benign	0.3369	benign	-1.935	Destabilizing	0.919	D	0.354	neutral	None	None	None	None	N
L/V	0.1007	likely_benign	0.0948	benign	-1.321	Destabilizing	0.103	N	0.177	neutral	N	0.47368874	None	None	N
L/W	0.3215	likely_benign	0.3954	ambiguous	-1.398	Destabilizing	0.999	D	0.532	neutral	None	None	None	None	N
L/Y	0.4786	ambiguous	0.5513	ambiguous	-1.203	Destabilizing	0.952	D	0.407	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.