TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21836	65731;65732;65733	chr2:178583676;178583675;178583674	chr2:179448403;179448402;179448401
N2AB	20195	60808;60809;60810	chr2:178583676;178583675;178583674	chr2:179448403;179448402;179448401
N2A	19268	58027;58028;58029	chr2:178583676;178583675;178583674	chr2:179448403;179448402;179448401
N2B	12771	38536;38537;38538	chr2:178583676;178583675;178583674	chr2:179448403;179448402;179448401
Novex-1	12896	38911;38912;38913	chr2:178583676;178583675;178583674	chr2:179448403;179448402;179448401
Novex-2	12963	39112;39113;39114	chr2:178583676;178583675;178583674	chr2:179448403;179448402;179448401
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Fn3-46
• Domain position: 80
• Structural Position: 110
• Q(SASA): 0.0647
• 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
A/V	None	None	0.955	D	0.667	0.59	0.712790429676	gnomAD-4.0.0	6.84941E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00012E-07	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
A/C	0.7578	likely_pathogenic	0.7135	pathogenic	-1.479	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
A/D	0.9982	likely_pathogenic	0.9979	pathogenic	-2.718	Highly Destabilizing	0.993	D	0.827	deleterious	D	0.560875416	None	None	N
A/E	0.9957	likely_pathogenic	0.9951	pathogenic	-2.462	Highly Destabilizing	0.995	D	0.807	deleterious	None	None	None	None	N
A/F	0.9744	likely_pathogenic	0.9731	pathogenic	-0.765	Destabilizing	0.998	D	0.875	deleterious	None	None	None	None	N
A/G	0.6308	likely_pathogenic	0.5632	ambiguous	-2.1	Highly Destabilizing	0.977	D	0.653	neutral	D	0.536730773	None	None	N
A/H	0.9957	likely_pathogenic	0.9956	pathogenic	-2.224	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
A/I	0.9231	likely_pathogenic	0.8673	pathogenic	-0.229	Destabilizing	0.995	D	0.821	deleterious	None	None	None	None	N
A/K	0.9985	likely_pathogenic	0.9985	pathogenic	-1.31	Destabilizing	0.995	D	0.819	deleterious	None	None	None	None	N
A/L	0.8284	likely_pathogenic	0.7745	pathogenic	-0.229	Destabilizing	0.966	D	0.759	deleterious	None	None	None	None	N
A/M	0.9448	likely_pathogenic	0.9071	pathogenic	-0.725	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
A/N	0.9926	likely_pathogenic	0.9904	pathogenic	-1.784	Destabilizing	0.995	D	0.829	deleterious	None	None	None	None	N
A/P	0.9754	likely_pathogenic	0.98	pathogenic	-0.651	Destabilizing	0.997	D	0.827	deleterious	D	0.549354526	None	None	N
A/Q	0.9862	likely_pathogenic	0.9854	pathogenic	-1.485	Destabilizing	0.998	D	0.843	deleterious	None	None	None	None	N
A/R	0.9905	likely_pathogenic	0.992	pathogenic	-1.487	Destabilizing	0.998	D	0.831	deleterious	None	None	None	None	N
A/S	0.4084	ambiguous	0.3377	benign	-2.18	Highly Destabilizing	0.955	D	0.631	neutral	D	0.525486145	None	None	N
A/T	0.6694	likely_pathogenic	0.4992	ambiguous	-1.797	Destabilizing	0.568	D	0.405	neutral	N	0.513369371	None	None	N
A/V	0.7065	likely_pathogenic	0.5699	pathogenic	-0.651	Destabilizing	0.955	D	0.667	neutral	D	0.540489755	None	None	N
A/W	0.9981	likely_pathogenic	0.9982	pathogenic	-1.452	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
A/Y	0.9932	likely_pathogenic	0.9936	pathogenic	-1.03	Destabilizing	1.0	D	0.877	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.