TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22950	69073;69074;69075	chr2:178577487;178577486;178577485	chr2:179442214;179442213;179442212
N2AB	21309	64150;64151;64152	chr2:178577487;178577486;178577485	chr2:179442214;179442213;179442212
N2A	20382	61369;61370;61371	chr2:178577487;178577486;178577485	chr2:179442214;179442213;179442212
N2B	13885	41878;41879;41880	chr2:178577487;178577486;178577485	chr2:179442214;179442213;179442212
Novex-1	14010	42253;42254;42255	chr2:178577487;178577486;178577485	chr2:179442214;179442213;179442212
Novex-2	14077	42454;42455;42456	chr2:178577487;178577486;178577485	chr2:179442214;179442213;179442212
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-128
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.3314
• 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
P/T	rs770007899	-0.921	0.491	N	0.377	0.226	0.307966526162	gnomAD-2.1.1	2.1E-05	None	None	None	None	N	None	0	0	None	0	2.82358E-04	None	0	None	0	0	0
P/T	rs770007899	-0.921	0.491	N	0.377	0.226	0.307966526162	gnomAD-4.0.0	4.17234E-06	None	None	None	None	N	None	0	0	None	0	1.53178E-04	None	0	0	0	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
P/A	0.1065	likely_benign	0.0939	benign	-0.408	Destabilizing	0.013	N	0.2	neutral	N	0.474467246	None	None	N
P/C	0.6499	likely_pathogenic	0.5941	pathogenic	-0.855	Destabilizing	0.991	D	0.488	neutral	None	None	None	None	N
P/D	0.4068	ambiguous	0.353	ambiguous	-0.312	Destabilizing	0.004	N	0.216	neutral	None	None	None	None	N
P/E	0.2884	likely_benign	0.2575	benign	-0.41	Destabilizing	0.017	N	0.21	neutral	None	None	None	None	N
P/F	0.6665	likely_pathogenic	0.6005	pathogenic	-0.713	Destabilizing	0.818	D	0.501	neutral	None	None	None	None	N
P/G	0.3541	ambiguous	0.3282	benign	-0.475	Destabilizing	0.345	N	0.406	neutral	None	None	None	None	N
P/H	0.2455	likely_benign	0.2051	benign	0.002	Stabilizing	0.873	D	0.46	neutral	N	0.514294851	None	None	N
P/I	0.4378	ambiguous	0.3793	ambiguous	-0.362	Destabilizing	0.39	N	0.456	neutral	None	None	None	None	N
P/K	0.3052	likely_benign	0.2655	benign	-0.434	Destabilizing	0.39	N	0.375	neutral	None	None	None	None	N
P/L	0.2028	likely_benign	0.1716	benign	-0.362	Destabilizing	0.326	N	0.422	neutral	N	0.513081343	None	None	N
P/M	0.3981	ambiguous	0.3425	ambiguous	-0.703	Destabilizing	0.901	D	0.465	neutral	None	None	None	None	N
P/N	0.3262	likely_benign	0.2905	benign	-0.274	Destabilizing	0.561	D	0.433	neutral	None	None	None	None	N
P/Q	0.1886	likely_benign	0.1646	benign	-0.444	Destabilizing	0.017	N	0.224	neutral	None	None	None	None	N
P/R	0.2334	likely_benign	0.2069	benign	-0.018	Destabilizing	0.326	N	0.47	neutral	N	0.475734694	None	None	N
P/S	0.1425	likely_benign	0.1271	benign	-0.595	Destabilizing	0.166	N	0.373	neutral	N	0.475481205	None	None	N
P/T	0.1308	likely_benign	0.112	benign	-0.601	Destabilizing	0.491	N	0.377	neutral	N	0.475481205	None	None	N
P/V	0.2874	likely_benign	0.245	benign	-0.351	Destabilizing	0.004	N	0.342	neutral	None	None	None	None	N
P/W	0.7682	likely_pathogenic	0.7278	pathogenic	-0.763	Destabilizing	0.991	D	0.544	neutral	None	None	None	None	N
P/Y	0.5552	ambiguous	0.4981	ambiguous	-0.509	Destabilizing	0.901	D	0.5	neutral	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.