TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10109	30550;30551;30552	chr2:178702562;178702561;178702560	chr2:179567289;179567288;179567287
N2AB	9792	29599;29600;29601	chr2:178702562;178702561;178702560	chr2:179567289;179567288;179567287
N2A	8865	26818;26819;26820	chr2:178702562;178702561;178702560	chr2:179567289;179567288;179567287
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-86
• Domain position: 32
• Structural Position: 47
• Q(SASA): 0.1731
• 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
T/A	rs2075197256	None	0.911	None	0.581	0.334	0.342631996419	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
T/A	0.4795	ambiguous	0.4797	ambiguous	-0.675	Destabilizing	0.911	D	0.581	neutral	None	None	None	None	N
T/C	0.9118	likely_pathogenic	0.9268	pathogenic	-0.34	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
T/D	0.9402	likely_pathogenic	0.943	pathogenic	-1.016	Destabilizing	0.985	D	0.729	prob.delet.	None	None	None	None	N
T/E	0.8801	likely_pathogenic	0.8939	pathogenic	-0.818	Destabilizing	0.985	D	0.722	prob.delet.	None	None	None	None	N
T/F	0.8757	likely_pathogenic	0.8811	pathogenic	-0.443	Destabilizing	0.999	D	0.786	deleterious	None	None	None	None	N
T/G	0.876	likely_pathogenic	0.8916	pathogenic	-1.068	Destabilizing	0.985	D	0.741	deleterious	None	None	None	None	N
T/H	0.7522	likely_pathogenic	0.7677	pathogenic	-1.092	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
T/I	0.7203	likely_pathogenic	0.7357	pathogenic	0.353	Stabilizing	0.997	D	0.746	deleterious	None	None	None	None	N
T/K	0.7144	likely_pathogenic	0.7253	pathogenic	-0.14	Destabilizing	0.98	D	0.726	prob.delet.	None	None	None	None	N
T/L	0.584	likely_pathogenic	0.5775	pathogenic	0.353	Stabilizing	0.993	D	0.715	prob.delet.	None	None	None	None	N
T/M	0.4233	ambiguous	0.4238	ambiguous	0.165	Stabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
T/N	0.6549	likely_pathogenic	0.6648	pathogenic	-0.836	Destabilizing	0.985	D	0.687	prob.neutral	None	None	None	None	N
T/P	0.9683	likely_pathogenic	0.9669	pathogenic	0.041	Stabilizing	0.997	D	0.751	deleterious	None	None	None	None	N
T/Q	0.7072	likely_pathogenic	0.7299	pathogenic	-0.596	Destabilizing	0.998	D	0.777	deleterious	None	None	None	None	N
T/R	0.684	likely_pathogenic	0.6782	pathogenic	-0.336	Destabilizing	0.997	D	0.763	deleterious	None	None	None	None	N
T/S	0.4633	ambiguous	0.4717	ambiguous	-1.056	Destabilizing	0.449	N	0.396	neutral	None	None	None	None	N
T/V	0.5836	likely_pathogenic	0.6128	pathogenic	0.041	Stabilizing	0.993	D	0.669	neutral	None	None	None	None	N
T/W	0.9636	likely_pathogenic	0.9698	pathogenic	-0.688	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
T/Y	0.8682	likely_pathogenic	0.8836	pathogenic	-0.223	Destabilizing	0.999	D	0.796	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.