NM_001130987.2(DYSF):c.4191C>A (p.Asn1397Lys) AND Qualitative or quantitative defects of dysferlin

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 21, 2022
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:: RCV002532620.2

Allele description [Variation Report for NM_001130987.2(DYSF):c.4191C>A (p.Asn1397Lys)]

NM_001130987.2(DYSF):c.4191C>A (p.Asn1397Lys)

Gene:

DYSF:dysferlin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p13.2

Genomic location:

Preferred name:

NM_001130987.2(DYSF):c.4191C>A (p.Asn1397Lys)

HGVS:

NC_000002.12:g.71611596C>A
NG_008694.1:g.162974C>A
NM_001130455.2:c.4140C>A
NM_001130976.2:c.4095C>A
NM_001130977.2:c.4095C>A
NM_001130978.2:c.4137C>A
NM_001130979.2:c.4230C>A
NM_001130980.2:c.4188C>A
NM_001130981.2:c.4188C>A
NM_001130982.2:c.4233C>A
NM_001130983.2:c.4140C>A
NM_001130984.2:c.4098C>A
NM_001130985.2:c.4191C>A
NM_001130986.2:c.4098C>A
NM_001130987.2:c.4191C>AMANE SELECT
NM_003494.3:c.4137C>A
NM_003494.4:c.4137C>A
NP_001123927.1:p.Asn1380Lys
NP_001124448.1:p.Asn1365Lys
NP_001124449.1:p.Asn1365Lys
NP_001124450.1:p.Asn1379Lys
NP_001124451.1:p.Asn1410Lys
NP_001124452.1:p.Asn1396Lys
NP_001124453.1:p.Asn1396Lys
NP_001124454.1:p.Asn1411Lys
NP_001124455.1:p.Asn1380Lys
NP_001124456.1:p.Asn1366Lys
NP_001124457.1:p.Asn1397Lys
NP_001124458.1:p.Asn1366Lys
NP_001124459.1:p.Asn1397Lys
NP_003485.1:p.Asn1379Lys
LRG_845t1:c.4137C>A
LRG_845t2:c.4191C>A
LRG_845:g.162974C>A
LRG_845p1:p.Asn1379Lys
LRG_845p2:p.Asn1397Lys
NC_000002.11:g.71838726C>A
NM_003494.4:c.4137C>A

Protein change:

N1365K

Links:

dbSNP: rs536906283

NCBI 1000 Genomes Browser:

rs536906283

Molecular consequence:

NM_001130455.2:c.4140C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130976.2:c.4095C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130977.2:c.4095C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130978.2:c.4137C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130979.2:c.4230C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130980.2:c.4188C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130981.2:c.4188C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130982.2:c.4233C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130983.2:c.4140C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130984.2:c.4098C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130985.2:c.4191C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130986.2:c.4098C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130987.2:c.4191C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_003494.4:c.4137C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Qualitative or quantitative defects of dysferlin
Synonyms:: Dysferlinopathy
Identifiers:: MONDO: MONDO:0016145; MedGen: C2931687

Recent activity

Clear Turn Off Turn On

Mus musculus zinc finger, MYND domain containing 19 (Zmynd19), transcript varian...
Mus musculus zinc finger, MYND domain containing 19 (Zmynd19), transcript variant 1, mRNA
gi|887230658|ref|NM_026021.4|

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003297139	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 21, 2022)	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

SCV003297139

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 21, 2022)

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	unknown	not provided	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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003297139.1

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

Description

This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 1379 of the DYSF protein (p.Asn1379Lys). This variant is present in population databases (rs536906283, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with DYSF-related conditions. ClinVar contains an entry for this variant (Variation ID: 501769). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt DYSF protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine