TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35335	106228;106229;106230	chr2:178530612;178530611;178530610	chr2:179395339;179395338;179395337
N2AB	33694	101305;101306;101307	chr2:178530612;178530611;178530610	chr2:179395339;179395338;179395337
N2A	32767	98524;98525;98526	chr2:178530612;178530611;178530610	chr2:179395339;179395338;179395337
N2B	26270	79033;79034;79035	chr2:178530612;178530611;178530610	chr2:179395339;179395338;179395337
Novex-1	26395	79408;79409;79410	chr2:178530612;178530611;178530610	chr2:179395339;179395338;179395337
Novex-2	26462	79609;79610;79611	chr2:178530612;178530611;178530610	chr2:179395339;179395338;179395337
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-165
• Domain position: 50
• Structural Position: 125
• Q(SASA): 0.5199
• 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
H/R	rs760807951	-0.636	1.0	N	0.583	0.403	0.410204130746	gnomAD-2.1.1	8.03E-06	None	None	None	None	N	None	0	0	None	0	1.11309E-04	None	0	None	0	0	0
H/R	rs760807951	-0.636	1.0	N	0.583	0.403	0.410204130746	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.92382E-04	None	0	0	0	0	0
H/R	rs760807951	-0.636	1.0	N	0.583	0.403	0.410204130746	gnomAD-4.0.0	7.68423E-06	None	None	None	None	N	None	0	0	None	0	1.21159E-04	None	0	0	2.39232E-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
H/A	0.52	ambiguous	0.5073	ambiguous	-0.183	Destabilizing	0.999	D	0.577	neutral	None	None	None	None	N
H/C	0.2442	likely_benign	0.2375	benign	0.416	Stabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
H/D	0.3846	ambiguous	0.3694	ambiguous	0.007	Stabilizing	1.0	D	0.651	neutral	N	0.500560337	None	None	N
H/E	0.4925	ambiguous	0.4864	ambiguous	0.072	Stabilizing	0.999	D	0.474	neutral	None	None	None	None	N
H/F	0.4609	ambiguous	0.4729	ambiguous	0.766	Stabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
H/G	0.5466	ambiguous	0.515	ambiguous	-0.517	Destabilizing	0.999	D	0.628	neutral	None	None	None	None	N
H/I	0.4491	ambiguous	0.4634	ambiguous	0.703	Stabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
H/K	0.4055	ambiguous	0.4009	ambiguous	-0.082	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	N
H/L	0.2077	likely_benign	0.2083	benign	0.703	Stabilizing	1.0	D	0.726	prob.delet.	N	0.498021464	None	None	N
H/M	0.741	likely_pathogenic	0.7489	pathogenic	0.475	Stabilizing	1.0	D	0.669	neutral	None	None	None	None	N
H/N	0.1533	likely_benign	0.1542	benign	-0.109	Destabilizing	0.999	D	0.467	neutral	N	0.509238535	None	None	N
H/P	0.7283	likely_pathogenic	0.639	pathogenic	0.432	Stabilizing	1.0	D	0.711	prob.delet.	N	0.514607069	None	None	N
H/Q	0.2951	likely_benign	0.29	benign	0.064	Stabilizing	1.0	D	0.623	neutral	N	0.513393561	None	None	N
H/R	0.1626	likely_benign	0.1518	benign	-0.641	Destabilizing	1.0	D	0.583	neutral	N	0.481974576	None	None	N
H/S	0.3243	likely_benign	0.3108	benign	-0.128	Destabilizing	1.0	D	0.646	neutral	None	None	None	None	N
H/T	0.4371	ambiguous	0.4405	ambiguous	0.045	Stabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
H/V	0.4517	ambiguous	0.4629	ambiguous	0.432	Stabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
H/W	0.596	likely_pathogenic	0.5656	pathogenic	0.945	Stabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
H/Y	0.1674	likely_benign	0.1629	benign	1.129	Stabilizing	0.999	D	0.477	neutral	N	0.498888255	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.