TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23059	69400;69401;69402	chr2:178577160;178577159;178577158	chr2:179441887;179441886;179441885
N2AB	21418	64477;64478;64479	chr2:178577160;178577159;178577158	chr2:179441887;179441886;179441885
N2A	20491	61696;61697;61698	chr2:178577160;178577159;178577158	chr2:179441887;179441886;179441885
N2B	13994	42205;42206;42207	chr2:178577160;178577159;178577158	chr2:179441887;179441886;179441885
Novex-1	14119	42580;42581;42582	chr2:178577160;178577159;178577158	chr2:179441887;179441886;179441885
Novex-2	14186	42781;42782;42783	chr2:178577160;178577159;178577158	chr2:179441887;179441886;179441885
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: Fn3-55
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.1156
• 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	rs1394979272	-1.598	0.988	D	0.675	0.408	0.62500370566	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
L/F	rs1394979272	-1.598	0.988	D	0.675	0.408	0.62500370566	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/F	rs1394979272	-1.598	0.988	D	0.675	0.408	0.62500370566	gnomAD-4.0.0	2.56464E-06	None	None	None	None	N	None	1.69314E-05	0	None	0	0	None	0	0	2.39498E-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
L/A	0.8803	likely_pathogenic	0.8929	pathogenic	-2.612	Highly Destabilizing	0.968	D	0.678	prob.neutral	None	None	None	None	N
L/C	0.7932	likely_pathogenic	0.8075	pathogenic	-1.942	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
L/D	0.9997	likely_pathogenic	0.9997	pathogenic	-3.337	Highly Destabilizing	0.998	D	0.893	deleterious	None	None	None	None	N
L/E	0.9976	likely_pathogenic	0.9979	pathogenic	-3.023	Highly Destabilizing	0.998	D	0.871	deleterious	None	None	None	None	N
L/F	0.4952	ambiguous	0.4752	ambiguous	-1.556	Destabilizing	0.988	D	0.675	prob.neutral	D	0.526252478	None	None	N
L/G	0.989	likely_pathogenic	0.9907	pathogenic	-3.231	Highly Destabilizing	0.995	D	0.861	deleterious	None	None	None	None	N
L/H	0.9917	likely_pathogenic	0.9926	pathogenic	-2.988	Highly Destabilizing	0.999	D	0.878	deleterious	D	0.570160444	None	None	N
L/I	0.0844	likely_benign	0.0816	benign	-0.769	Destabilizing	0.142	N	0.322	neutral	N	0.475263714	None	None	N
L/K	0.9963	likely_pathogenic	0.9968	pathogenic	-2.023	Highly Destabilizing	0.995	D	0.831	deleterious	None	None	None	None	N
L/M	0.2556	likely_benign	0.2576	benign	-0.938	Destabilizing	0.991	D	0.655	neutral	None	None	None	None	N
L/N	0.9977	likely_pathogenic	0.9978	pathogenic	-2.672	Highly Destabilizing	0.998	D	0.897	deleterious	None	None	None	None	N
L/P	0.9971	likely_pathogenic	0.9975	pathogenic	-1.371	Destabilizing	0.998	D	0.893	deleterious	D	0.570160444	None	None	N
L/Q	0.9881	likely_pathogenic	0.9899	pathogenic	-2.344	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
L/R	0.9907	likely_pathogenic	0.9921	pathogenic	-2.039	Highly Destabilizing	0.998	D	0.87	deleterious	D	0.570160444	None	None	N
L/S	0.9912	likely_pathogenic	0.992	pathogenic	-3.277	Highly Destabilizing	0.995	D	0.834	deleterious	None	None	None	None	N
L/T	0.9526	likely_pathogenic	0.9579	pathogenic	-2.796	Highly Destabilizing	0.991	D	0.676	prob.neutral	None	None	None	None	N
L/V	0.0833	likely_benign	0.0811	benign	-1.371	Destabilizing	0.618	D	0.597	neutral	N	0.520676532	None	None	N
L/W	0.9696	likely_pathogenic	0.9693	pathogenic	-2.049	Highly Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
L/Y	0.9677	likely_pathogenic	0.9678	pathogenic	-1.753	Destabilizing	0.995	D	0.765	deleterious	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.