NM_144573.4(NEXN):c.1937C>A (p.Pro646Gln) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 1, 2011
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000041168.5

Allele description [Variation Report for NM_144573.4(NEXN):c.1937C>A (p.Pro646Gln)]

NM_144573.4(NEXN):c.1937C>A (p.Pro646Gln)

Gene:

NEXN:nexilin F-actin binding protein [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p31.1

Genomic location:

Preferred name:

NM_144573.4(NEXN):c.1937C>A (p.Pro646Gln)

HGVS:

NC_000001.11:g.77942738C>A
NG_016625.1:g.59224C>A
NG_033243.2:g.41356G>T
NM_001172309.2:c.1745C>A
NM_144573.4:c.1937C>AMANE SELECT
NP_001165780.1:p.Pro582Gln
NP_653174.3:p.Pro646Gln
NP_653174.3:p.Pro646Gln
LRG_442t1:c.1937C>A
LRG_442:g.59224C>A
LRG_442p1:p.Pro646Gln
LRG_995:g.41356G>T
NC_000001.10:g.78408423C>A
NM_144573.3:c.1937C>A
c.1937C>A

Protein change:

P582Q

Links:

dbSNP: rs397517852

NCBI 1000 Genomes Browser:

rs397517852

Molecular consequence:

NM_001172309.2:c.1745C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_144573.4:c.1937C>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000064859	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Uncertain significance (Nov 1, 2011)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000064859

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Uncertain significance
(Nov 1, 2011)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	1	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000064859.6

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

Description

The Pro646Gln variant has not been previously reported but has been identified b y our laboratory in 1 individual with HCM. Proline (Pro) at position 646 is high ly conserved across evolutionarily distant species, increasing the likelihood th at a change would not be tolerated. In addition, computational tools (AlignGVGD, PolyPhen2, and SIFT) predict that this change will impact the protein, though t heir accuracy is unknown. Although this data increases the likelihood that this variant is pathogenic, it should be noted that the NEXN gene has not yet been wi dely sequenced. It therefore remains possible that this variant will turn out to be common in the general population once a larger number of individuals have be en sequenced. In summary, additional data is needed to determine the clinical si gnificance of this variant.

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

Last Updated: Dec 24, 2022

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