NM_139027.6(ADAMTS13):c.1370C>T (p.Pro457Leu) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Jan 18, 2024
Review status:: criteria provided, conflicting classifications

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000886026.14

Allele description [Variation Report for NM_139027.6(ADAMTS13):c.1370C>T (p.Pro457Leu)]

NM_139027.6(ADAMTS13):c.1370C>T (p.Pro457Leu)

Gene:

ADAMTS13:ADAM metallopeptidase with thrombospondin type 1 motif 13 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q34.2

Genomic location:

Preferred name:

NM_139027.6(ADAMTS13):c.1370C>T (p.Pro457Leu)

HGVS:

NC_000009.12:g.133436890C>T
NG_011934.2:g.27552C>T
NM_139025.5:c.1370C>T
NM_139026.6:c.1277C>T
NM_139027.6:c.1370C>TMANE SELECT
NP_620594.1:p.Pro457Leu
NP_620594.1:p.Pro457Leu
NP_620595.1:p.Pro426Leu
NP_620596.2:p.Pro457Leu
LRG_544t1:c.1370C>T
LRG_544:g.27552C>T
LRG_544p1:p.Pro457Leu
NC_000009.11:g.136302010C>T
NC_000009.11:g.136302010C>T
NM_139025.3:c.1370C>T
NM_139025.4:c.1370C>T
NM_139027.6:c.1370C>T
Q76LX8:p.Pro457Leu

Protein change:

P426L

Links:

UniProtKB: Q76LX8#VAR_027163; dbSNP: rs36220240

NCBI 1000 Genomes Browser:

rs36220240

Molecular consequence:

NM_139025.5:c.1370C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_139026.6:c.1277C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_139027.6:c.1370C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001029509	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely benign (Jan 18, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001713515	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Oct 18, 2022)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 12753286, 17627784, 1787257, 19847791, 23878316, 28866379, 30046676, 25741868
SCV002757284	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Nov 10, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001029509

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely benign
(Jan 18, 2024)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001713515

Mayo Clinic Laboratories, Mayo Clinic

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Oct 18, 2022)

germline

clinical testing

PubMed (8)
[See all records that cite these PMIDs]

SCV002757284

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Nov 10, 2022)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	6	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Mutation analysis and clinical implications of von Willebrand factor-cleaving protease deficiency.

Assink K, Schiphorst R, Allford S, Karpman D, Etzioni A, Brichard B, van de Kar N, Monnens L, van den Heuvel L.

Kidney Int. 2003 Jun;63(6):1995-9.

PubMed [citation]

PMID:: 12753286

See all PubMed Citations (9)

Details of each submission

From Invitae, SCV001029509.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Mayo Clinic Laboratories, Mayo Clinic, SCV001713515.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	6	not provided	not provided	clinical testing	PubMed (8)

Description

BS1, PS3_supporting

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		6	not provided	not provided	not provided

From GeneDx, SCV002757284.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Published functional studies demonstrate a damaging effect with impaired secretion and reduced enzyme activity (Manea et al., 2007b; Katneni et al., 2017); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28866379, 21228398, 23346910, 17187257, 34426522, 28748566, 32183147, 32531546, 30046676, 17627784, 12753286)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 19, 2024

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