TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15709	47350;47351;47352	chr2:178618333;178618332;178618331	chr2:179483060;179483059;179483058
N2AB	14068	42427;42428;42429	chr2:178618333;178618332;178618331	chr2:179483060;179483059;179483058
N2A	13141	39646;39647;39648	chr2:178618333;178618332;178618331	chr2:179483060;179483059;179483058
N2B	6644	20155;20156;20157	chr2:178618333;178618332;178618331	chr2:179483060;179483059;179483058
Novex-1	6769	20530;20531;20532	chr2:178618333;178618332;178618331	chr2:179483060;179483059;179483058
Novex-2	6836	20731;20732;20733	chr2:178618333;178618332;178618331	chr2:179483060;179483059;179483058
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-1
• Domain position: 53
• Structural Position: 70
• Q(SASA): 0.5924
• 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
D/V	None	None	0.999	N	0.831	0.479	0.433713641954	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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
D/A	0.607	likely_pathogenic	0.5416	ambiguous	-0.532	Destabilizing	0.999	D	0.755	deleterious	N	0.465927869	None	None	N
D/C	0.9545	likely_pathogenic	0.9236	pathogenic	-0.054	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
D/E	0.3719	ambiguous	0.3379	benign	-0.477	Destabilizing	0.767	D	0.263	neutral	N	0.462194465	None	None	N
D/F	0.9486	likely_pathogenic	0.9282	pathogenic	-0.402	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
D/G	0.5677	likely_pathogenic	0.4939	ambiguous	-0.774	Destabilizing	0.998	D	0.741	deleterious	D	0.523971718	None	None	N
D/H	0.781	likely_pathogenic	0.7248	pathogenic	-0.486	Destabilizing	1.0	D	0.771	deleterious	D	0.549224988	None	None	N
D/I	0.8836	likely_pathogenic	0.8641	pathogenic	0.073	Stabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
D/K	0.8468	likely_pathogenic	0.791	pathogenic	0.064	Stabilizing	0.999	D	0.74	deleterious	None	None	None	None	N
D/L	0.8539	likely_pathogenic	0.8103	pathogenic	0.073	Stabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
D/M	0.939	likely_pathogenic	0.9168	pathogenic	0.381	Stabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
D/N	0.2532	likely_benign	0.2082	benign	-0.271	Destabilizing	0.999	D	0.699	prob.neutral	N	0.463559752	None	None	N
D/P	0.9034	likely_pathogenic	0.8616	pathogenic	-0.106	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
D/Q	0.7588	likely_pathogenic	0.7024	pathogenic	-0.231	Destabilizing	0.999	D	0.741	deleterious	None	None	None	None	N
D/R	0.8542	likely_pathogenic	0.8212	pathogenic	0.188	Stabilizing	0.999	D	0.805	deleterious	None	None	None	None	N
D/S	0.3433	ambiguous	0.2883	benign	-0.41	Destabilizing	0.997	D	0.676	prob.neutral	None	None	None	None	N
D/T	0.6213	likely_pathogenic	0.5716	pathogenic	-0.221	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
D/V	0.7315	likely_pathogenic	0.6959	pathogenic	-0.106	Destabilizing	0.999	D	0.831	deleterious	N	0.454988536	None	None	N
D/W	0.9828	likely_pathogenic	0.9769	pathogenic	-0.224	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
D/Y	0.7536	likely_pathogenic	0.6897	pathogenic	-0.159	Destabilizing	1.0	D	0.825	deleterious	D	0.559434602	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.